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 C. Maggio, Renzo Marcolongo, Francesco La TorreClaudia Fabiani, Serena Colafrancesco, Francesca Ricci, Paola Galozzi, Ombretta Viapiana, Elena Verrecchia, Manuela Pardeo, Lucia Cerrito, Elena Cavallaro, Alma N. 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, 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology)

Research output: Contribution to journalArticle

35 Citations (Scopus)

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: 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.

Original languageEnglish
Article number380
JournalFrontiers in Pharmacology
Volume7
Issue numberOCT
DOIs
Publication statusPublished - Oct 24 2016

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Interleukin 1 Receptor Antagonist Protein
Off-Label Use
Interleukin-1
Italy
Observational Studies
Retrospective Studies
Pediatrics
Antirheumatic Agents
Rheumatologists
Therapeutics
canakinumab
Adrenal Cortex Hormones
Demography
Delivery of Health Care
Physicians
Safety
Weights and Measures

Keywords

  • Anakinra
  • Autoinflammatory disorders
  • Canakinumab
  • Interleukin (IL)-1
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Vitale, A., Insalaco, A., Sfriso, P., Lopalco, G., Emmi, G., Cattalini, M., ... 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology) (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. Frontiers in Pharmacology, 7(OCT), [380]. https://doi.org/10.3389/fphar.2016.00380

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. / 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; 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology).

In: Frontiers in Pharmacology, Vol. 7, No. OCT, 380, 24.10.2016.

Research output: Contribution to journalArticle

Vitale, A, Insalaco, A, Sfriso, P, Lopalco, G, Emmi, G, Cattalini, M, Manna, R, Cimaz, R, Priori, R, Talarico, R, Gentileschi, S, de Marchi, G, Frassi, M, Gallizzi, R, Soriano, A, Alessio, M, Cammelli, D, Maggio, MC, Marcolongo, R, La Torre, F, Fabiani, C, Colafrancesco, S, Ricci, F, Galozzi, P, Viapiana, O, Verrecchia, E, Pardeo, M, Cerrito, L, Cavallaro, E, Olivieri, AN, Paolazzi, G, Vitiello, G, Maier, A, Silvestri, E, Stagnaro, C, Valesini, G, Mosca, M, de Vita, S, Tincani, A, Lapadula, G, Frediani, B, De Benedetti, F, Iannone, F, Punzi, L, Salvarani, C, Galeazzi, M, Rigante, D, Cantarini, L & 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology) 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', Frontiers in Pharmacology, vol. 7, no. OCT, 380. https://doi.org/10.3389/fphar.2016.00380
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 ; 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology). / 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. In: Frontiers in Pharmacology. 2016 ; Vol. 7, No. OCT.
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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",
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: 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.",
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author = "Antonio Vitale and Antonella Insalaco and Paolo Sfriso and Giuseppe Lopalco and Giacomo Emmi and Marco Cattalini and Raffaele Manna and Rolando Cimaz and Roberta Priori and Rosaria Talarico and Stefano Gentileschi and {de Marchi}, Ginevra and Micol Frassi and Romina Gallizzi and Alessandra Soriano and Maria Alessio and Daniele Cammelli and Maggio, {Maria C.} and Renzo Marcolongo and {La Torre}, Francesco and Claudia Fabiani and Serena Colafrancesco and Francesca Ricci and Paola Galozzi and Ombretta Viapiana and Elena Verrecchia and Manuela Pardeo and Lucia Cerrito and Elena Cavallaro and Olivieri, {Alma N.} and Giuseppe Paolazzi and Gianfranco Vitiello and Armin Maier and Elena Silvestri and Chiara Stagnaro and Guido Valesini and Marta Mosca and {de Vita}, Salvatore and Angela Tincani and Giovanni Lapadula and Bruno Frediani and {De Benedetti}, Fabrizio and Florenzo Iannone and Leonardo Punzi and Carlo Salvarani and Mauro Galeazzi and Donato Rigante and Luca Cantarini and {'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology)}",
year = "2016",
month = "10",
day = "24",
doi = "10.3389/fphar.2016.00380",
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journal = "Frontiers in Pharmacology",
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number = "OCT",

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TY - JOUR

T1 - A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists

T2 - A nationwide multi-center retrospective observational study

AU - Vitale, Antonio

AU - Insalaco, Antonella

AU - Sfriso, Paolo

AU - Lopalco, Giuseppe

AU - Emmi, Giacomo

AU - Cattalini, Marco

AU - Manna, Raffaele

AU - Cimaz, Rolando

AU - Priori, Roberta

AU - Talarico, Rosaria

AU - Gentileschi, Stefano

AU - de Marchi, Ginevra

AU - Frassi, Micol

AU - Gallizzi, Romina

AU - Soriano, Alessandra

AU - Alessio, Maria

AU - Cammelli, Daniele

AU - Maggio, Maria C.

AU - Marcolongo, Renzo

AU - La Torre, Francesco

AU - Fabiani, Claudia

AU - Colafrancesco, Serena

AU - Ricci, Francesca

AU - Galozzi, Paola

AU - Viapiana, Ombretta

AU - Verrecchia, Elena

AU - Pardeo, Manuela

AU - Cerrito, Lucia

AU - Cavallaro, Elena

AU - Olivieri, Alma N.

AU - Paolazzi, Giuseppe

AU - Vitiello, Gianfranco

AU - Maier, Armin

AU - Silvestri, Elena

AU - Stagnaro, Chiara

AU - Valesini, Guido

AU - Mosca, Marta

AU - de Vita, Salvatore

AU - Tincani, Angela

AU - Lapadula, Giovanni

AU - Frediani, Bruno

AU - De Benedetti, Fabrizio

AU - Iannone, Florenzo

AU - Punzi, Leonardo

AU - Salvarani, Carlo

AU - Galeazzi, Mauro

AU - Rigante, Donato

AU - Cantarini, Luca

AU - 'Working Group' of Systemic Autoinflammatory Diseases of SIR (Italian Society of Rheumatology)

PY - 2016/10/24

Y1 - 2016/10/24

N2 - 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.

AB - 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.

KW - Anakinra

KW - Autoinflammatory disorders

KW - Canakinumab

KW - Interleukin (IL)-1

KW - Treatment

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