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15-06-2016 | Juvenile idiopathic arthritis | Review | Article

Biologics in Pediatric Rheumatology: Quo Vadis?

Journal: Current Rheumatology Reports

Authors: Yonit Sterba, Norman Ilowite

Publisher: Springer US

Abstract

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.
Literature
1.
Barnes MG, Grom AA, Thompson SD, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60(7):2102–12. doi:10.​1002/​art.​24601.CrossRefPubMedPubMedCentral
2.
Mangge H, Kenzian H, Gallistl S. Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum. 1995;38(2):211–20.CrossRefPubMed
3.
Berard RA, Laxer RM. Etanercept (enbrel) in the treatment of juvenile idiopathic arthritis. Expert Opin Biol Ther. 2013;13(11):1623–30. doi:10.​1517/​14712598.​2013.​840580.CrossRefPubMed
4.
Ungar WJ, Costa V, Burnett HF, et al. The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: a systematic review. Semin Arthritis Rheum. 2013;42(6):597–618. doi:10.​1016/​j.​semarthrit.​2012.​10.​006.CrossRefPubMed
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.CrossRefPubMed
6.
Bernatsky S, Rosenberg AM, Oen KG, Duffy CM, Ramsey-Goldman R, Labrecque J, et al. Malignancies in juvenile idiopathic arthritis: a preliminary report. J Rheumatol. 2011;38(4):760–3. doi:10.​3899/​jrheum.​100711.CrossRefPubMed
7.
Lovell DJ, Giannini EH, Reiff A, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric rheumatology collaborative study group. N Engl J Med. 2000;342(11):763–9. doi:10.​1056/​NEJM200003163421​103.CrossRefPubMed
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.CrossRefPubMed
9.
Prince FHM, Geerdink LM, Borsboom GJJM, et al. Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2010;69(01):138–42. doi:10.​1136/​ard.​2009.​111260.CrossRefPubMed
10.
Halbig M, Horneff G. Improvement of functional ability in children with juvenile idiopathic arthritis by treatment with etanercept. Rheumatol Int. 2009;30(2):229–38. doi:10.​1007/​s00296-009-0942-3.CrossRefPubMed
11.
Nicolino R, Lovell DJ, Cuttica R, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56(9):3096–106. doi:10.​1002/​art.​22838.CrossRef
12.••
Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359(8):810–20. doi:10.​1056/​NEJMoa0706290. Initial study showing efficacy of Adalimumab.CrossRefPubMed
13.
García-De-Vicuña C, Díaz-Llopis M, Salom D, et al. Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. Mediat Inflamm. 2013;2013:1–6. doi:10.​1155/​2013/​560632.CrossRef
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.CrossRef
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.CrossRef
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.
17.
Pascual V. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201(9):1479–86. doi:10.​1084/​jem.​20050473.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
19.
Nigrovic PA, Mannion M, Prince FH, et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011;63(2):545–55. doi:10.​1002/​art.​30128.CrossRefPubMed
20.•
Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355(6):581–92. doi:10.​1056/​NEJMoa055137. Only anakinra trial in NOMID.CrossRefPubMedPubMedCentral
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.CrossRef
22.
Lovell DJ, Giannini EH, Reiff AO, et al. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis: rilonacept for systemic juvenile idiopathic arthritis. Arthritis Rheum. 2013;65(9):2486–96. doi:10.​1002/​art.​38042.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
24.
De Benedetti F, Brunner HI, Nicolino R, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2385–95. doi:10.​1056/​NEJMoa1112802.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRef
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.CrossRef
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.CrossRefPubMed
30.
Alexeeva EI, Valieva SI, Bzarova TM, et al. Efficacy and safety of repeat courses of rituximab treatment in patients with severe refractory juvenile idiopathic arthritis. Clin Rheumatol. 2011;30(9):1163–72. doi:10.​1007/​s10067-011-1720-7.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
32.
Baird EM, Lehman TJA, Worgall S. Combination therapy with rituximab and cyclophosphamide in the treatment of anti-neutrophil cytoplasmic antibodies (ANCA) positive pulmonary hemorrhage: case report. Pediatric Rheumatol. 2011;9(1):33. doi:10.​1186/​1546-0096-9-33.CrossRef
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.CrossRef
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.
35.
Bader-Meunier B, Decaluwe H, Barnerias C, et al. Safety and efficacy of rituximab in severe juvenile dermatomyositis: results from 9 patients from the French Autoimmunity and Rituximab Registry. J Rheumatol. 2011;38(7):1436–40. doi:10.​3899/​jrheum.​101321.CrossRefPubMed
36.
Hui-Yuen JS, Reddy A, Taylor J, Li X, et al. Safety and efficacy of belimumab to treat systemic lupus erythematosus in academic clinical practices. J Rheumatol. 2015;42(12):2288–95. doi:10.​3899/​jrheum.​150470.CrossRefPubMed
37.
Ruperto N, Lovell DJ, Quartier P, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383–91. doi:10.​1016/​S0140-6736(08)60998-8.CrossRefPubMed
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.
39.
Foell D. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA. 2010;303(13):1266. doi:10.​1001/​jama.​2010.​375.CrossRefPubMed
40.
Moncrieffe H, Ursu S, Holzinger D, et al. A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein. Rheumatology (Oxford, England). 2013;52(8):1467–76. doi:10.​1093/​rheumatology/​ket152.CrossRef
41.
Cobb J, Cule E, Moncrieffe H, et al. Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. Pharmacogenomics J. 2014;14(4):356–64. doi:10.​1038/​tpj.​2014.​3.CrossRefPubMedPubMedCentral
42.
Bulatovic M, Heijstek MW, Van Dijkhuizen EHP, et al. Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis. Ann Rheum Dis. 2012;71(9):1484–9. doi:10.​1136/​annrheumdis-2011-200942.CrossRefPubMed