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.

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, 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, M. C.; Marcolongo, R.; La Torre, F.; Fabiani, C.; Colafrancesco, S.; Ricci, F.; Galozzi, P.; Viapiana, O.; Verrecchia, E.; Pardeo, M.; Cerrito, L.; Cavallaro, E.; Olivieri, A. N.; 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.. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 7:OCT(2016), p. 380. [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

Soriano A.;Alessio M.;La Torre F.;Silvestri E.;Punzi L.;
2016

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.
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 / 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, M. C.; Marcolongo, R.; La Torre, F.; Fabiani, C.; Colafrancesco, S.; Ricci, F.; Galozzi, P.; Viapiana, O.; Verrecchia, E.; Pardeo, M.; Cerrito, L.; Cavallaro, E.; Olivieri, A. N.; 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.. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 7:OCT(2016), p. 380. [10.3389/fphar.2016.00380]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/821340
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