Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial

Fecha de publicación: 01/06/2015

Autores de IIS La Fe

Inmaculada Calvo Penadés

Autor

Participantes ajenos a IIS La Fe

Brunner HI
Ruperto N
Zuber Z
Keane C
Harari O
Kenwright A
Lu P
Cuttica R
Keltsev V
Xavier RM
Nikishina I
Rubio-Pérez N
Alexeeva E
Chasnyk V
Horneff G
Opoka-Winiarska V
Quartier P
Silva CA
Silverman E
Spindler A
Baildam E
Gámir ML
Martin A
Rietschel C
Siri D
Smolewska E
Lovell D
Martini A
De Benedetti F
Paediatric Rheumatology International Trials Organisation PRINTO
Pediatric Rheumatology Collaborative Study Group (PRCSG)

Grupos

Reumatología Pediátrica

Investigador establecido

Inmaculada Calvo Penadés

Abstract

Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for 6months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4weeks (8 or 10mg/kg for body weight (BW) <30kg; 8mg/kg for BW 30kg). At week 16, patients with JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30kg: 10mg/kg (n=35) or 8mg/kg (n=34); 30kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.

Datos de la publicación

ISSN/ISSNe:: 0003-4967, 1468-2060
Tipo:: Article
Páginas:: 1110-1117
DOI:: 10.1136/annrheumdis-2014-205351
Factor de Impacto:: 5,909 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Brunner HI:: Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA
Ruperto N:: Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy
Zuber Z:: Department of Pediatric Neurology and Rheumatology, St. Louis Children's Hospital, Cracow, Poland
Keane C:: Roche Products Ltd, Welwyn Garden City, UK
Harari O:: Roche Products Ltd, Welwyn Garden City, UK
Kenwright A:: Roche Products Ltd, Welwyn Garden City, UK
Lu P:: Roche, Nutley, New Jersey, USA
Cuttica R:: Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina
Keltsev V:: Department of Pediatric Cardiology and Rheumatology, Samara Regional Clinical Hospital, Samara, Russia
Xavier RM:: Rheumatology Service, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Calvo I:: Paediatric Rheumatology Department, Hospital Universitario La Fe, Valencia, Spain
Nikishina I:: Pediatric Department, Federal State Budgetary Institution (Research Institute of Rheumatology named after V.A. Nasonova) under the Russian Academy of Medical Sciences, Moscow, Russia
Rubio-Pérez N:: Department of Pediatrics, Hospital Universitario, Universidad Autónoma de Nuevo León, Nuevo León, Mexico
Alexeeva E:: Scientific Center, Children's Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russia
Chasnyk V:: St Petersburg State Pediatric Medical Academy, St Petersburg, Russia
Horneff G:: Asklepios Klinik Sankt Augustin, Centre for General Pediatrics and Neonatology, Sankt Augustin, Germany
Opoka-Winiarska V:: Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, Lublin, Poland
Quartier P:: Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades and Institut IMAGINE, Paris, France
Silva CA:: Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, Children's Institute, São Paulo, Brazil
Silverman E:: Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
Spindler A:: Department of Medicine, Universidad Nacional de Tucumán, Tucumán, Argentina
Baildam E:: Department of Paediatric Rheumatology, Alder Hey Children's Foundation NHS Trust, Liverpool, UK
Gámir ML:: Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain
Martin A:: Tulsa Bone & Joint Associates, Tulsa, Oklahoma, USA
Rietschel C:: Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhäuser, Frankfurt, Germany
Siri D:: CAICI Institute, Rosario, Argentina
Smolewska E:: Department of Pediatric Cardiology and Rheumatology, Medical University of Lódz, Lódz, Poland
Lovell D:: Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA
Martini A:: Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy Dipartimento di Pediatria, Università di Genova, Genoa, Italy
De Benedetti F:: Ospedale Pediatrico Bambino Gesù, Rome, Italy