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Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.

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

Author information

1
Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA.
2
Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy.
3
Department of Pediatric Neurology and Rheumatology, St. Louis Children's Hospital, Cracow, Poland.
4
Roche Products Ltd, Welwyn Garden City, UK.
5
Roche, Nutley, New Jersey, USA.
6
Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina.
7
Department of Pediatric Cardiology and Rheumatology, Samara Regional Clinical Hospital, Samara, Russia.
8
Rheumatology Service, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
9
Paediatric Rheumatology Department, Hospital Universitario La Fe, Valencia, Spain.
10
Pediatric Department, Federal State Budgetary Institution (Research Institute of Rheumatology named after V.A. Nasonova) under the Russian Academy of Medical Sciences, Moscow, Russia.
11
Department of Pediatrics, Hospital Universitario, Universidad Autónoma de Nuevo León, Nuevo León, Mexico.
12
Scientific Center, Children's Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russia.
13
St Petersburg State Pediatric Medical Academy, St Petersburg, Russia.
14
Asklepios Klinik Sankt Augustin, Centre for General Pediatrics and Neonatology, Sankt Augustin, Germany.
15
Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, Lublin, Poland.
16
Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades and Institut IMAGINE, Paris, France.
17
Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, Children's Institute, São Paulo, Brazil.
18
Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
19
Department of Medicine, Universidad Nacional de Tucumán, Tucumán, Argentina.
20
Department of Paediatric Rheumatology, Alder Hey Children's Foundation NHS Trust, Liverpool, UK.
21
Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
22
Tulsa Bone & Joint Associates, Tulsa, Oklahoma, USA.
23
Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhäuser, Frankfurt, Germany.
24
CAICI Institute, Rosario, Argentina.
25
Department of Pediatric Cardiology and Rheumatology, Medical University of Łódź, Łódź, Poland.
26
Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy Dipartimento di Pediatria, Università di Genova, Genoa, Italy.
27
Ospedale Pediatrico Bambino Gesù, Rome, Italy.

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 ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). 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 (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: 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.

KEYWORDS:

DMARDs (biologic); Juvenile Idiopathic Arthritis; Treatment

PMID:
24834925
PMCID:
PMC4431348
DOI:
10.1136/annrheumdis-2014-205351
[Indexed for MEDLINE]
Free PMC Article
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