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


BACKGROUND
NCT00988221.
Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA.
Hermine I
HI
Brunner
Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy.
Nicolino
N
Ruperto
Department of Pediatric Neurology and Rheumatology, St. Louis Children's Hospital, Cracow, Poland.
Zbigniew
Z
Zuber
Roche Products Ltd, Welwyn Garden City, UK.
Caroline
C
Keane
Roche Products Ltd, Welwyn Garden City, UK.
Olivier
O
Harari
Roche Products Ltd, Welwyn Garden City, UK.
Andrew
A
Kenwright
Roche, Nutley, New Jersey, USA.
Peng
P
Lu
Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina.
Ruben
R
Cuttica
Department of Pediatric Cardiology and Rheumatology, Samara Regional Clinical Hospital, Samara, Russia.
Vladimir
V
Keltsev
Rheumatology Service, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Ricardo M
RM
Xavier
Paediatric Rheumatology Department, Hospital Universitario La Fe, Valencia, Spain.
Inmaculada
I
Calvo
Pediatric Department, Federal State Budgetary Institution (Research Institute of Rheumatology named after V.A. Nasonova) under the Russian Academy of Medical Sciences, Moscow, Russia.
Irina
I
Nikishina
Department of Pediatrics, Hospital Universitario, Universidad Autónoma de Nuevo León, Nuevo León, Mexico.
Nadina
N
Rubio-Pérez
Scientific Center, Children's Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russia.
Ekaterina
E
Alexeeva
St Petersburg State Pediatric Medical Academy, St Petersburg, Russia.
Vyacheslav
V
Chasnyk
Asklepios Klinik Sankt Augustin, Centre for General Pediatrics and Neonatology, Sankt Augustin, Germany.
Gerd
G
Horneff
Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, Lublin, Poland.
Violetta
V
Opoka-Winiarska
Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades and Institut IMAGINE, Paris, France.
Pierre
P
Quartier
Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, Children's Institute, São Paulo, Brazil.
Clovis A
CA
Silva
Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Earl
E
Silverman
Department of Medicine, Universidad Nacional de Tucumán, Tucumán, Argentina.
Alberto
A
Spindler
Department of Paediatric Rheumatology, Alder Hey Children's Foundation NHS Trust, Liverpool, UK.
Eileen
E
Baildam
Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
M Luz
ML
Gámir
Tulsa Bone & Joint Associates, Tulsa, Oklahoma, USA.
Alan
A
Martin
Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhäuser, Frankfurt, Germany.
Christoph
C
Rietschel
CAICI Institute, Rosario, Argentina.
Daniel
D
Siri
Department of Pediatric Cardiology and Rheumatology, Medical University of Łódź, Łódź, Poland.
Elzbieta
E
Smolewska
Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA.
Daniel
D
Lovell
Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy Dipartimento di Pediatria, Università di Genova, Genoa, Italy.
Alberto
A
Martini
Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Fabrizio
F
De Benedetti
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001991:Bronchitis / Q000139:chemically induced; D002481:Cellulitis / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D011014:Pneumonia / Q000139:chemically induced; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019947:Receptors, Interleukin-6; C502936:tocilizumab; D008727:Methotrexate
DMARDs (biologic); Juvenile Idiopathic Arthritis; Treatment