title: Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept.
abstract: BACKGROUND
  Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN).
  
  
  METHODS
  In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment.
  
  
  RESULTS
  1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis.
  
  
  CONCLUSIONS
  Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.
authors.affiliation: Università degli Studi di Genova, Genova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Verazza
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Davì
authors.affiliation: Università degli Studi di Genova, Genova, Italy.|Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Consolaro
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bovis
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Insalaco
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Magni-Manzoni
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nicolai
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Denise Pires
authors.initials: DP
authors.lastname: Marafon
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.affiliation: Istituto Ortopedico Gaetano Pini, Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Gerloni
authors.affiliation: Istituto Ortopedico Gaetano Pini, Milano, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pontikaki
authors.affiliation: Istituto Ortopedico Gaetano Pini, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rovelli
authors.affiliation: Ospedale Pediatrico Meyer, Firenze, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.affiliation: Ospedale Pediatrico Meyer, Firenze, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Marino
authors.affiliation: Università degli Studi, Padova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zulian
authors.affiliation: Università degli Studi, Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Martini
authors.affiliation: IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pastore
authors.affiliation: IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sandrin
authors.affiliation: Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Corona
authors.affiliation: Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Torcoletti
authors.affiliation: Azienda Ospedaliera Universitaria Policlinico G. Martino, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Conti
authors.affiliation: Azienda Ospedaliera Universitaria Policlinico G. Martino, Messina, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fede
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico Vittorio Emanuele, Catania, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Barone
authors.affiliation: Università degli Studi di Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cattalini
authors.affiliation: Ospedale di Orvieto, Orvieto, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cortis
authors.affiliation: Università degli Studi di Chieti, Chieti, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Breda
authors.affiliation: Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Alma Nunzia
authors.initials: AN
authors.lastname: Olivieri
authors.affiliation: Azienda Ospedaliera Card. G. Panico, Tricase, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Civino
authors.affiliation: Ospedale Regionale per le Microcitemie, Cagliari, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Podda
authors.affiliation: Policlinico Universitario A. Gemelli, Roma, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Rigante
authors.affiliation: Ospedale A. Perrino, Brindisi, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: La Torre
authors.affiliation: Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: D'Angelo
authors.affiliation: Ospedale Pediatrico G. Salesi, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Jorini
authors.affiliation: Università degli Studi di Messina, Messina, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Gallizzi
authors.affiliation: Ospedale dei Bambini G. Di Cristina, Palermo, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Maggio
authors.affiliation: Università degli Studi di Pisa, Pisa, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Consolini
authors.affiliation: Arcispedale S.Maria Nuova, Reggio Emilia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Fanti
authors.affiliation: IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Muratore
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Maria Giannina
authors.initials: MG
authors.lastname: Alpigiani
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Nicolino
authors.initials: N
authors.lastname: Ruperto
authors.affiliation: Università degli Studi di Genova, Genova, Italy.|Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.affiliation: Università degli Studi di Genova, Genova, Italy. angeloravelli@gaslini.org.|Istituto Giannina Gaslini, Genova, Italy. angeloravelli@gaslini.org.|Pediatria II-Reumatologia, Istituto G. Gaslini, Largo G. Gaslini 5, 16147, Genova, Italy. angeloravelli@gaslini.org.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ravelli
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D057915:Drug Substitution; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D063868:Patient Outcome Assessment; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000068800:Etanercept; D008727:Methotrexate
keywords: Biologic therapies; Etanercept; Juvenile idiopathic arthritis; Pediatric rheumatology; TNF inhibitors