Article Text

Extended report
Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial
  1. Hermine I Brunner1,
  2. Nicolino Ruperto2,
  3. Nikolay Tzaribachev3,
  4. Gerd Horneff4,
  5. Vyacheslav G Chasnyk5,
  6. Violeta Panaviene6,
  7. Carlos Abud-Mendoza7,
  8. Andreas Reiff8,
  9. Ekaterina Alexeeva9,
  10. Nadina Rubio-Pérez10,
  11. Vladimir Keltsev11,
  12. Daniel J Kingsbury12,
  13. Maria del Rocio Maldonado Velázquez13,
  14. Irina Nikishina14,
  15. Earl D Silverman15,
  16. Rik Joos16,
  17. Elzbieta Smolewska17,
  18. Márcia Bandeira18,
  19. Kirsten Minden19,
  20. Annet van Royen-Kerkhof20,
  21. Wolfgang Emminger21,
  22. Ivan Foeldvari22,
  23. Bernard R Lauwerys23,
  24. Flavio Sztajnbok24,
  25. Keith E Gilmer25,
  26. Zhenhua Xu25,
  27. Jocelyn H Leu25,
  28. Lilianne Kim25,
  29. Sarah L Lamberth25,
  30. Matthew J Loza25,
  31. Daniel J Lovell1,
  32. Alberto Martini2
  33. for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)
  1. 1 Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
  2. 2 Istituto Giannina Gaslini, Pediatria II - Rheumatologia, PRINTO, Genoa, Italy
  3. 3 Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany
  4. 4 Department of Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany
  5. 5 Hospital Pediatry, State Pediatric Medical Academy, Saint Petersburg, Russian Federation
  6. 6 Centre of Pediatrics, Vilnius University, Vilnius, Lithuania
  7. 7 Regional Unit of Rheumatology and Osteoporosis, Central Hospital “Dr. Ignacio Morones Prieto” and Faculty of Medicine, Universidad Autónoma de San Luis Potosí, Mexico, San Luis Potosí, Mexico
  8. 8 Department of Rheumatology, Children’s Hospital of Los Angeles, Los Angeles, California, USA
  9. 9 Children’s Health of RAMS and IM Sechenov First Moscow State Medical University, Moscow, Russian Federation
  10. 10 Hospital Universitario, Universidad Autónoma de Nuevo León, Nuevo León, Mexico
  11. 11 Samara Regional Clinical Hospital, Samara, Russian Federation
  12. 12 Randall Children’s Hospital at Legacy Emanuel, Portland, Oregon, USA
  13. 13 Hospital Infantil de Mexico Federico Gomez, Distrito Federal, Mexico
  14. 14 Pediatric Department, V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation
  15. 15 Department of Rheumatology, The Hospital for Sick Children, Toronto, Canada
  16. 16 ZNA Jan Palfijn, Antwerpen, Belgium
  17. 17 Medical University of Łódź, Łódź, Poland
  18. 18 Hospital Pequeno Principe, Curitiba, Brazil
  19. 19 Department of Pediatric Rheumatology, Charité University Medicine, Berlin, Germany
  20. 20 Department of Paediatric Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  21. 21 University Children’s Hospital, Wien, Austria
  22. 22 Klinikum Eilbek, Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany
  23. 23 Pôle de pathologies rhumatismales systémiques et inflammatoires, Université catholique de Louvain, Institut de Recherche Clinique, Brussels, Belgium
  24. 24 Nucleo de Estudos da Saúde do Adolescente, Hospital Universitario Pedro Ernesto, Rio de Janeiro, Brazil
  25. 25 Janssen Research & Development, LLC, Spring House, Pennsylvania, USA
  1. Correspondence to Dr Hermine I Brunner, Cincinnati Children’s Hospital Medical Center, PRCSG Coordinating Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3930, USA; Hermine.brunner{at}cchmc.org

Abstract

Objective This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).

Methods In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0–16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16–48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.

Results Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA.

Conclusion Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.

Clinical Trial Registration NCT01230827; Results.

  • juvenile idiopathic arthritis
  • anti-tumour necrosis factor
  • golimumab
  • biologics

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Footnotes

  • HIB and NR contributed equally.

  • Contributors Study design: HIB, NR, AM, DJL; data collection and/or analysis: HIB, NR, NT, GH, VGC, VP, CAM, AR, EA, NRP, VK, DJK, MRMV, IN, EDS, RJ, ES, MB, KM, ARK, WE, IF, BRL, FS, KEG, ZX, JHL, LK, SLL, MJL, DJL, AM; manuscript: All authors drafted and/or revised the manuscript and approved the manuscript for submission.

  • Funding This study was funded by Janssen Research & Development, LLC, a wholly owned subsidiary of Johnson & Johnson, and Merck/Schering-Plough.

  • Competing interests HIB has served as a consultant and steering committee member for Janssen Research & Development, a consultant for AstraZeneca, Pfizer and Takeda and received research support from Novartis, Roche and UCB. NR served on the speaker’s bureau and as a consultant for AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, F. Hoffmann-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and UCB Biosciences GmbH. DJL has served as a consultant for Boehringer Ingelheim, Celgene, Janssen Research & Development and Novartis, as a trial investigator for AbbVie, Bristol-Myers Squibb, Janssen Research & Development, Roche, Pfizer and UBC and received research support from the National Institutes of Health. NRP received fees from AbbVie and Roche. FS received research support from Janssen. KM received research support from Pfizer, AbbVie, Roche and Deutsche Kinder-Rheumastiftung and fees from AbbVie, Genzyme, Medac, Pfizer and Pharm-Allergan. IN received fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer and Roche and grants from Pfizer and Roche. EA received research support from AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer and Roche and fees from AbbVie, Bristol-Myers Squibb, Medac, Merck Sharp & Dohme, Novartis, Pfizer and Roche. KEG, ZX, JHL, LK, SLL and MJL are employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson. AM received speaking and consulting fees from AbbVie, Boehringer, Celgene, CrescendoBio, Janssen, MedImmune, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex and Servier. Nothing to disclose: NT, GH, VGC, CAM, AR, DJK, EDS, VP, MRMV, ES, MB, ARK, VK, RJ, WE, IF, BRL.

  • Ethics approval Institutional Review Board or Ethics Committee at each site.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The PRINTO and PRCSG statement has been added to the list of authors.

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