Biologics in Pediatric Rheumatology: Quo Vadis?
- 626 Downloads
The past two decades have brought immense satisfaction to pediatric rheumatologists and families of children with rheumatologic diseases. We have been able to better classify, recognize, and diagnose rheumatologic diseases, but most importantly, the discovery of biologic therapies and their efficacy and relative safety in treating multiple rheumatologic conditions, improving quality of life for the patients we care for. We will review the advances of the past two decades and discuss potential areas for new discoveries.
KeywordsTNF inhibitors IL-1 inhibitors IL-6 inhibitors Abatacept Rituximab Tofacitinib Juvenile idiopathic arthritis (JIA)
Compliance with Ethics Standards
Conflict of Interest
YS declares that she has no conflict of interest. NI reports funding from Novartis, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 5.•Guzman J, Kiem O, Tucker LB, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015;74(10):1854–60. doi: 10.1136/annrheumdis-2014-205372. This is one of the few articles that discusses outcomes in the era of DMARDs.CrossRefPubMedGoogle Scholar
- 8.Otten MH, Anink J, Prince FH, et al. Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national arthritis and biologics in children register. Ann Rheum Dis. 2015;74(7):1379–86. doi: 10.1136/annrheumdis-2013-204641.CrossRefPubMedGoogle Scholar
- 14.Gabriele S, Taddio A, Cattalini M, et al. Superior efficacy of adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis. Pediatr Rheumatol. 2013;11(1):16. doi: 10.1186/1546-0096-11-16.CrossRefGoogle Scholar
- 15.•Brunner, Hermine N, Ruperto N, Tzaribachev G, et al. A148: A multi-center, double-blind, randomized-withdrawal trial of subcutaneous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy: week 48 results. Arthritis Rheum. 2014;66:S191–92. doi: 10.1002/art.38569. First golimumab trial in pediatric rheumatology.CrossRefGoogle Scholar
- 16.•Pediatric Arthritis Study of Certolizumab Pegol (PASCAL). Available from:https://clinicaltrials.gov/ct2/show/study/NCT01550003?show_locs=Y%23locn. Initial trial of certolizumab in pediatric rheumatology- unpublished results.
- 18.•Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54. doi: 10.1136/ard.2010.134254. Initial anakinra trial in SJIA.CrossRefPubMedGoogle Scholar
- 21.••Nicolino R, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396–406. doi: 10.1056/NEJMoa1205099. This articles includes data from the two canakinumab studies that lead to its FDA approval for SJIA.CrossRefGoogle Scholar
- 23.Ilowite NT, Kristi P, Yuliya L, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis: rilonacept in the treatment of systemic JIA. Arthritis Rheumatol. 2014;66(9):2570–9. doi: 10.1002/art.38699.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.••Brunner HI, Nicolino R, Zbigniew Z, et al. 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;74(6):1110–7. doi: 10.1136/annrheumdis-2014-205351. Newest data to support use of tocilizumab in polyarticular course JIA.CrossRefPubMedGoogle Scholar
- 26.Kavanaugh A, Lluís P, Gottlieb AB, et al. Maintenance of clinical efficacy and radiographic benefit through two years of ustekinumab therapy in patients with active psoriatic arthritis: results from a randomized, placebo-controlled phase III trial. Arthritis Care Res. 2015;67(12):1739–49. doi: 10.1002/acr.22645.CrossRefGoogle Scholar
- 27.McInnes IB, Arthur K, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet (London, England). 2013;382(9894):780–9. doi: 10.1016/S0140-6736(13)60594-2.CrossRefGoogle Scholar
- 28.Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional Non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheumatic Dis. 2014;73(6):990–9. doi: 10.1136/annrheumdis-2013-204655.CrossRefGoogle Scholar
- 29.Poddubnyy D, Hermann K-GA, Callhoff J, et al. Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014;73(5):817–23. doi: 10.1136/annrheumdis-2013-204248.CrossRefPubMedGoogle Scholar
- 31.•Dale RC, Brilot F, Duffy LV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology. 2014;83(2):142–50. doi: 10.1212/WNL.0000000000000570. This is a retrospective study showing better outcomes in patients with autoinflammatory brain disease treated with rituximab.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.•Lehman TJ, Singh C, Ramanathan A, et al. Prolonged improvement of childhood onset systemic lupus erythematosus following systematic administration of rituximab and cyclophosphamide. Pediatric Rheumatol. 2014;12(1):3. doi: 10.1186/1546-0096-12-3. This articles provides an alternative and innovative approach in difficult to treat SLE patients.CrossRefGoogle Scholar
- 34.Cassidy Petty, Ross E, Ronald M Laxer, Carol B Lindsley, Lucy Wedderburn, and James T Cassidy. Textbook of pediatric rheumatology, 2016. http://www.sciencedirect.com/science/book/9780323241458.
- 38.••Pharmacokinetics of CP-690 550 in pediatric patients with juvenile idiopathic arthritis (JIA) NCT01513902 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT01513902. Ongoing trail of Tofacitinib in JIA which could provide an oral biologic alternative.