Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis
- PMID: 23252525
- DOI: 10.1056/NEJMoa1112802
Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis
Erratum in
- N Engl J Med. 2015 Feb 26;372(9):887
Abstract
Background: Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA.
Methods: We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension.
Results: At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range.
Conclusions: Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.).
Comment in
-
A new era in the treatment of systemic juvenile idiopathic arthritis.N Engl J Med. 2012 Dec 20;367(25):2439-40. doi: 10.1056/NEJMe1212640. N Engl J Med. 2012. PMID: 23252530 No abstract available.
-
Paediatric rheumatology: Biologic therapy for systemic juvenile idiopathic arthritis--times they are a'changing!Nat Rev Rheumatol. 2013 Feb;9(2):63. doi: 10.1038/nrrheum.2013.2. Epub 2013 Jan 15. Nat Rev Rheumatol. 2013. PMID: 23321610 No abstract available.
-
Tocilizumab for systemic juvenile idiopathic arthritis.N Engl J Med. 2013 Mar 28;368(13):1256-7. doi: 10.1056/NEJMc1301017. N Engl J Med. 2013. PMID: 23534566 No abstract available.
-
Tocilizumab for systemic juvenile idiopathic arthritis.N Engl J Med. 2013 Mar 28;368(13):1256. doi: 10.1056/NEJMc1301017. N Engl J Med. 2013. PMID: 23534567 No abstract available.
Similar articles
-
Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.N Engl J Med. 2012 Dec 20;367(25):2396-406. doi: 10.1056/NEJMoa1205099. N Engl J Med. 2012. PMID: 23252526 Clinical Trial.
-
Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial.Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16. Ann Rheum Dis. 2015. PMID: 24834925 Free PMC article. Clinical Trial.
-
Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis.Paediatr Drugs. 2013 Dec;15(6):515-31. doi: 10.1007/s40272-013-0053-1. Paediatr Drugs. 2013. PMID: 24155139 Review.
-
Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial.Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7. Lancet. 2008. PMID: 18358927 Clinical Trial.
-
The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation.Health Technol Assess. 2016 Apr;20(34):1-222. doi: 10.3310/hta20340. Health Technol Assess. 2016. PMID: 27135404 Free PMC article. Review.
Cited by
-
Histological Assessment of Respiratory Tract and Liver of BALB/c Mice Nebulized with Tocilizumab.Pharmaceutics. 2024 Jun 27;16(7):862. doi: 10.3390/pharmaceutics16070862. Pharmaceutics. 2024. PMID: 39065559 Free PMC article.
-
Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.Medicine (Baltimore). 2024 May 3;103(18):e38002. doi: 10.1097/MD.0000000000038002. Medicine (Baltimore). 2024. PMID: 38701278 Free PMC article.
-
Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study.World J Clin Pediatr. 2024 Mar 9;13(1):88912. doi: 10.5409/wjcp.v13.i1.88912. eCollection 2024 Mar 9. World J Clin Pediatr. 2024. PMID: 38596441 Free PMC article.
-
Concordance and agreement between different activity scores in polymyalgia rheumatica.RMD Open. 2024 Mar 15;10(1):e003741. doi: 10.1136/rmdopen-2023-003741. RMD Open. 2024. PMID: 38490696 Free PMC article. Clinical Trial.
-
Adult-Onset Still's Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options.Drugs. 2024 Mar;84(3):257-274. doi: 10.1007/s40265-024-01993-x. Epub 2024 Mar 5. Drugs. 2024. PMID: 38441807 Free PMC article. Review.
Publication types
MeSH terms
Substances
Supplementary concepts
Associated data
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous