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

To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).
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.
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).
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.
AuthorsHermine I Brunner, Nicolino Ruperto, Zbigniew Zuber, Caroline Keane, Olivier Harari, Andrew Kenwright, Peng Lu, Ruben Cuttica, Vladimir Keltsev, Ricardo M Xavier, Inmaculada Calvo, Irina Nikishina, Nadina Rubio-Pérez, Ekaterina Alexeeva, Vyacheslav Chasnyk, Gerd Horneff, Violetta Opoka-Winiarska, Pierre Quartier, Clovis A Silva, Earl Silverman, Alberto Spindler, Eileen Baildam, M Luz Gámir, Alan Martin, Christoph Rietschel, Daniel Siri, Elzbieta Smolewska, Daniel Lovell, Alberto Martini, Fabrizio De Benedetti, ,
JournalAnnals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 6 Pg. 1110-7 (Jun 2015) ISSN: 1468-2060 [Electronic] England
PMID24834925 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
CopyrightPublished by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Chemical References
  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Receptors, Interleukin-6
  • tocilizumab
  • Methotrexate
  • Adolescent
  • Adrenal Cortex Hormones (therapeutic use)
  • Antibodies, Monoclonal, Humanized (therapeutic use)
  • Antirheumatic Agents (therapeutic use)
  • Arthritis, Juvenile (drug therapy)
  • Bronchitis (chemically induced)
  • Cellulitis (chemically induced)
  • Child
  • Child, Preschool
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Maintenance Chemotherapy (methods)
  • Male
  • Methotrexate (therapeutic use)
  • Pneumonia (chemically induced)
  • Receptors, Interleukin-6 (antagonists & inhibitors)
  • Remission Induction (methods)
  • Treatment Outcome

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