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Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial
  1. Hermine I Brunner1,
  2. Nicolino Ruperto2,
  3. Zbigniew Zuber3,
  4. Caroline Keane4,
  5. Olivier Harari4,
  6. Andrew Kenwright4,
  7. Peng Lu5,
  8. Ruben Cuttica6,
  9. Vladimir Keltsev7,
  10. Ricardo M Xavier8,
  11. Inmaculada Calvo9,
  12. Irina Nikishina10,
  13. Nadina Rubio-Pérez11,
  14. Ekaterina Alexeeva12,
  15. Vyacheslav Chasnyk13,
  16. Gerd Horneff14,
  17. Violetta Opoka-Winiarska15,
  18. Pierre Quartier16,
  19. Clovis A Silva17,
  20. Earl Silverman18,
  21. Alberto Spindler19,
  22. Eileen Baildam20,
  23. M Luz Gámir21,
  24. Alan Martin22,
  25. Christoph Rietschel23,
  26. Daniel Siri24,
  27. Elzbieta Smolewska25,
  28. Daniel Lovell1,
  29. Alberto Martini2,26,
  30. Fabrizio De Benedetti27,
  31. for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)
  1. 1Division of Rheumatology, Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, PRCSG Coordinating Center, Cincinnati, Ohio, USA
  2. 2Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy
  3. 3Department of Pediatric Neurology and Rheumatology, St. Louis Children's Hospital, Cracow, Poland
  4. 4Roche Products Ltd, Welwyn Garden City, UK
  5. 5Roche, Nutley, New Jersey, USA
  6. 6Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina
  7. 7Department of Pediatric Cardiology and Rheumatology, Samara Regional Clinical Hospital, Samara, Russia
  8. 8Rheumatology Service, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  9. 9Paediatric Rheumatology Department, Hospital Universitario La Fe, Valencia, Spain
  10. 10Pediatric Department, Federal State Budgetary Institution (Research Institute of Rheumatology named after V.A. Nasonova) under the Russian Academy of Medical Sciences, Moscow, Russia
  11. 11Department of Pediatrics, Hospital Universitario, Universidad Autónoma de Nuevo León, Nuevo León, Mexico
  12. 12Scientific Center, Children's Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russia
  13. 13St Petersburg State Pediatric Medical Academy, St Petersburg, Russia
  14. 14Asklepios Klinik Sankt Augustin, Centre for General Pediatrics and Neonatology, Sankt Augustin, Germany
  15. 15Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, Lublin, Poland
  16. 16Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades and Institut IMAGINE, Paris, France
  17. 17Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, Children's Institute, São Paulo, Brazil
  18. 18Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
  19. 19Department of Medicine, Universidad Nacional de Tucumán, Tucumán, Argentina
  20. 20Department of Paediatric Rheumatology, Alder Hey Children's Foundation NHS Trust, Liverpool, UK
  21. 21Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain
  22. 22Tulsa Bone & Joint Associates, Tulsa, Oklahoma, USA
  23. 23Clementine Kinderhospital, Verein Frankfurter Stiftungskrankenhäuser, Frankfurt, Germany
  24. 24CAICI Institute, Rosario, Argentina
  25. 25Department of Pediatric Cardiology and Rheumatology, Medical University of Łódź, Łódź, Poland
  26. 26Dipartimento di Pediatria, Università di Genova, Genoa, Italy
  27. 27Ospedale Pediatrico Bambino Gesù, Rome, Italy
  1. Correspondence to Dr Hermine I Brunner, Cincinnati Children's Hospital Medical Center, Division of Rheumatology and the Anderson Center for Excellence in Health Care, PRCSG Coordinating Center, MC 4010, 3333 Burnet Avenue, Cincinnati, OH 45229-3930, USA; Hermine.brunner{at}cchmc.org

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.

  • DMARDs (biologic)
  • Juvenile Idiopathic Arthritis
  • Treatment

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