Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease

Jurgen Sota, Donato Rigante, Piero Ruscitti, Antonella Insalaco, Paolo Sfriso, Salvatore De Vita, Rolando Cimaz, Giuseppe Lopalco, Giacomo Emmi, Francesco La Torre, Claudia Fabiani, Alma Nunzia Olivieri, Marco Cattalini, Daniele Cammelli, Romina Gallizzi, Maria Alessio, Raffaele Manna, Ombretta Viapiana, Micol Frassi, Manuela PardeoArmin Maier, Carlo Salvarani, Rosaria Talarico, Marta Mosca, Serena Colafrancesco, Roberta Priori, Maria Cristina Maggio, Carla Gaggiano, Salvatore Grosso, Fabrizio De Benedetti, Antonio Vitale, Roberto Giacomelli, Luca Cantarini

Research output: Contribution to journalArticle

Abstract

Background and objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult onset Still disease (AOSD). Herein we report on the effectiveness of Anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and methods: This is a multicentre study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48- and 60-months of follow-up was 74.3%, 62.9%, 49.4% and 49.4%, respectively, though without any significant differences between sJIA and AOSD patients (p=0.164), and between patients treated in monotherapy compared with the subgroup co-administered with conventional disease modifying anti-rheumatic drugs (cDMARDs) (p=0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p=0.009), which persisted even after adjustment for pathology (p=0.013). In the regression analysis, patients experiencing adverse events (AEs) (HR=3.029 [C.I. 1.750-5.242], p<0.0001) and those previously treated with other biologic agents (HR=1.818 [C.I. 1.007-3.282], p=0.047) were associated with a higher hazard ratio of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p<0.0001). Significant corticosteroid-sparing (p=0.033) and cDMARD-sparing effects (p<0.0001) were also recorded. Less than 1/3 of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant other drug-sparing effect and showed an overall good safety profile.

Original languageEnglish
Article number918
JournalFrontiers in Pharmacology
Volume10
Issue numberJULY
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Adult-Onset Still's Disease
Interleukin 1 Receptor Antagonist Protein
Juvenile Arthritis
Pharmaceutical Preparations
Antirheumatic Agents
Interleukin-1
Biological Factors
Patient Safety
Biological Products
Tertiary Care Centers
Multicenter Studies
Medical Records
Adrenal Cortex Hormones
Regression Analysis
Pathology
Safety
Skin

Keywords

  • Adult onset Still disease
  • Anakinra
  • Drug retention rate
  • Innovative biotechnologies
  • Interleukin 1-beta
  • Personalized medicine
  • Systemic juvenile idiopathic arthritis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease. / Sota, Jurgen; Rigante, Donato; Ruscitti, Piero; Insalaco, Antonella; Sfriso, Paolo; De Vita, Salvatore; Cimaz, Rolando; Lopalco, Giuseppe; Emmi, Giacomo; Torre, Francesco La; Fabiani, Claudia; Olivieri, Alma Nunzia; Cattalini, Marco; Cammelli, Daniele; Gallizzi, Romina; Alessio, Maria; Manna, Raffaele; Viapiana, Ombretta; Frassi, Micol; Pardeo, Manuela; Maier, Armin; Salvarani, Carlo; Talarico, Rosaria; Mosca, Marta; Colafrancesco, Serena; Priori, Roberta; Maggio, Maria Cristina; Gaggiano, Carla; Grosso, Salvatore; De Benedetti, Fabrizio; Vitale, Antonio; Giacomelli, Roberto; Cantarini, Luca.

In: Frontiers in Pharmacology, Vol. 10, No. JULY, 918, 01.01.2019.

Research output: Contribution to journalArticle

Sota, J, Rigante, D, Ruscitti, P, Insalaco, A, Sfriso, P, De Vita, S, Cimaz, R, Lopalco, G, Emmi, G, Torre, FL, Fabiani, C, Olivieri, AN, Cattalini, M, Cammelli, D, Gallizzi, R, Alessio, M, Manna, R, Viapiana, O, Frassi, M, Pardeo, M, Maier, A, Salvarani, C, Talarico, R, Mosca, M, Colafrancesco, S, Priori, R, Maggio, MC, Gaggiano, C, Grosso, S, De Benedetti, F, Vitale, A, Giacomelli, R & Cantarini, L 2019, 'Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease', Frontiers in Pharmacology, vol. 10, no. JULY, 918. https://doi.org/10.3389/fphar.2019.00918
Sota, Jurgen ; Rigante, Donato ; Ruscitti, Piero ; Insalaco, Antonella ; Sfriso, Paolo ; De Vita, Salvatore ; Cimaz, Rolando ; Lopalco, Giuseppe ; Emmi, Giacomo ; Torre, Francesco La ; Fabiani, Claudia ; Olivieri, Alma Nunzia ; Cattalini, Marco ; Cammelli, Daniele ; Gallizzi, Romina ; Alessio, Maria ; Manna, Raffaele ; Viapiana, Ombretta ; Frassi, Micol ; Pardeo, Manuela ; Maier, Armin ; Salvarani, Carlo ; Talarico, Rosaria ; Mosca, Marta ; Colafrancesco, Serena ; Priori, Roberta ; Maggio, Maria Cristina ; Gaggiano, Carla ; Grosso, Salvatore ; De Benedetti, Fabrizio ; Vitale, Antonio ; Giacomelli, Roberto ; Cantarini, Luca. / Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease. In: Frontiers in Pharmacology. 2019 ; Vol. 10, No. JULY.
@article{39002dbb47e54febbaff8f8beed7c8a7,
title = "Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease",
abstract = "Background and objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult onset Still disease (AOSD). Herein we report on the effectiveness of Anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and methods: This is a multicentre study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48- and 60-months of follow-up was 74.3{\%}, 62.9{\%}, 49.4{\%} and 49.4{\%}, respectively, though without any significant differences between sJIA and AOSD patients (p=0.164), and between patients treated in monotherapy compared with the subgroup co-administered with conventional disease modifying anti-rheumatic drugs (cDMARDs) (p=0.473). On the other hand, a significant difference in DRR was found between biologic-na{\"i}ve patients and those previously treated with biotechnologic drugs (p=0.009), which persisted even after adjustment for pathology (p=0.013). In the regression analysis, patients experiencing adverse events (AEs) (HR=3.029 [C.I. 1.750-5.242], p<0.0001) and those previously treated with other biologic agents (HR=1.818 [C.I. 1.007-3.282], p=0.047) were associated with a higher hazard ratio of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p<0.0001). Significant corticosteroid-sparing (p=0.033) and cDMARD-sparing effects (p<0.0001) were also recorded. Less than 1/3 of our cohort developed AEs, and 85{\%} were deemed mild in nature, with 70{\%} of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant other drug-sparing effect and showed an overall good safety profile.",
keywords = "Adult onset Still disease, Anakinra, Drug retention rate, Innovative biotechnologies, Interleukin 1-beta, Personalized medicine, Systemic juvenile idiopathic arthritis",
author = "Jurgen Sota and Donato Rigante and Piero Ruscitti and Antonella Insalaco and Paolo Sfriso and {De Vita}, Salvatore and Rolando Cimaz and Giuseppe Lopalco and Giacomo Emmi and Torre, {Francesco La} and Claudia Fabiani and Olivieri, {Alma Nunzia} and Marco Cattalini and Daniele Cammelli and Romina Gallizzi and Maria Alessio and Raffaele Manna and Ombretta Viapiana and Micol Frassi and Manuela Pardeo and Armin Maier and Carlo Salvarani and Rosaria Talarico and Marta Mosca and Serena Colafrancesco and Roberta Priori and Maggio, {Maria Cristina} and Carla Gaggiano and Salvatore Grosso and {De Benedetti}, Fabrizio and Antonio Vitale and Roberto Giacomelli and Luca Cantarini",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fphar.2019.00918",
language = "English",
volume = "10",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",
number = "JULY",

}

TY - JOUR

T1 - Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease

AU - Sota, Jurgen

AU - Rigante, Donato

AU - Ruscitti, Piero

AU - Insalaco, Antonella

AU - Sfriso, Paolo

AU - De Vita, Salvatore

AU - Cimaz, Rolando

AU - Lopalco, Giuseppe

AU - Emmi, Giacomo

AU - Torre, Francesco La

AU - Fabiani, Claudia

AU - Olivieri, Alma Nunzia

AU - Cattalini, Marco

AU - Cammelli, Daniele

AU - Gallizzi, Romina

AU - Alessio, Maria

AU - Manna, Raffaele

AU - Viapiana, Ombretta

AU - Frassi, Micol

AU - Pardeo, Manuela

AU - Maier, Armin

AU - Salvarani, Carlo

AU - Talarico, Rosaria

AU - Mosca, Marta

AU - Colafrancesco, Serena

AU - Priori, Roberta

AU - Maggio, Maria Cristina

AU - Gaggiano, Carla

AU - Grosso, Salvatore

AU - De Benedetti, Fabrizio

AU - Vitale, Antonio

AU - Giacomelli, Roberto

AU - Cantarini, Luca

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background and objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult onset Still disease (AOSD). Herein we report on the effectiveness of Anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and methods: This is a multicentre study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48- and 60-months of follow-up was 74.3%, 62.9%, 49.4% and 49.4%, respectively, though without any significant differences between sJIA and AOSD patients (p=0.164), and between patients treated in monotherapy compared with the subgroup co-administered with conventional disease modifying anti-rheumatic drugs (cDMARDs) (p=0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p=0.009), which persisted even after adjustment for pathology (p=0.013). In the regression analysis, patients experiencing adverse events (AEs) (HR=3.029 [C.I. 1.750-5.242], p<0.0001) and those previously treated with other biologic agents (HR=1.818 [C.I. 1.007-3.282], p=0.047) were associated with a higher hazard ratio of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p<0.0001). Significant corticosteroid-sparing (p=0.033) and cDMARD-sparing effects (p<0.0001) were also recorded. Less than 1/3 of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant other drug-sparing effect and showed an overall good safety profile.

AB - Background and objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult onset Still disease (AOSD). Herein we report on the effectiveness of Anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and methods: This is a multicentre study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48- and 60-months of follow-up was 74.3%, 62.9%, 49.4% and 49.4%, respectively, though without any significant differences between sJIA and AOSD patients (p=0.164), and between patients treated in monotherapy compared with the subgroup co-administered with conventional disease modifying anti-rheumatic drugs (cDMARDs) (p=0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p=0.009), which persisted even after adjustment for pathology (p=0.013). In the regression analysis, patients experiencing adverse events (AEs) (HR=3.029 [C.I. 1.750-5.242], p<0.0001) and those previously treated with other biologic agents (HR=1.818 [C.I. 1.007-3.282], p=0.047) were associated with a higher hazard ratio of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p<0.0001). Significant corticosteroid-sparing (p=0.033) and cDMARD-sparing effects (p<0.0001) were also recorded. Less than 1/3 of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant other drug-sparing effect and showed an overall good safety profile.

KW - Adult onset Still disease

KW - Anakinra

KW - Drug retention rate

KW - Innovative biotechnologies

KW - Interleukin 1-beta

KW - Personalized medicine

KW - Systemic juvenile idiopathic arthritis

UR - http://www.scopus.com/inward/record.url?scp=85070677702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070677702&partnerID=8YFLogxK

U2 - 10.3389/fphar.2019.00918

DO - 10.3389/fphar.2019.00918

M3 - Article

AN - SCOPUS:85070677702

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - JULY

M1 - 918

ER -