Skip to main content
Top
Published in: Clinical Rheumatology 1/2008

01-01-2008 | Original Article

Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence

Authors: Gerald Gartlehner, Richard A. Hansen, Beth L. Jonas, Patricia Thieda, Kathleen N. Lohr

Published in: Clinical Rheumatology | Issue 1/2008

Login to get access

Abstract

Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA.
Literature
1.
go back to reference Manners PJ, Bower C (2002) Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol 29(7):1520–1530PubMed Manners PJ, Bower C (2002) Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol 29(7):1520–1530PubMed
3.
go back to reference Andersson Gare B (1999) Juvenile arthritis—who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatol 17(3):367–374PubMed Andersson Gare B (1999) Juvenile arthritis—who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatol 17(3):367–374PubMed
4.
go back to reference Newacheck PW, Taylor WR (1992) Childhood chronic illness: prevalence, severity, and impact. Am J Public Health 82(3):364–371PubMedCrossRef Newacheck PW, Taylor WR (1992) Childhood chronic illness: prevalence, severity, and impact. Am J Public Health 82(3):364–371PubMedCrossRef
5.
go back to reference Thompson SD, Moroldo MB, Guyer L et al (2004) A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis Rheum 50(9):2920–2930PubMedCrossRef Thompson SD, Moroldo MB, Guyer L et al (2004) A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis Rheum 50(9):2920–2930PubMedCrossRef
6.
go back to reference Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392PubMed Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392PubMed
7.
go back to reference Hashkes PJ, Laxer RM (2005) Medical treatment of juvenile idiopathic arthritis. JAMA 294(13):1671–1684PubMedCrossRef Hashkes PJ, Laxer RM (2005) Medical treatment of juvenile idiopathic arthritis. JAMA 294(13):1671–1684PubMedCrossRef
8.
go back to reference Minden K, Kiessling U, Listing J et al (2000) Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol 27(9):2256–2263PubMed Minden K, Kiessling U, Listing J et al (2000) Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol 27(9):2256–2263PubMed
9.
go back to reference Wilkinson N, Jackson G, Gardner-Medwin J (2003) Biologic therapies for juvenile arthritis. Arch Dis Child 88(3):186–191PubMedCrossRef Wilkinson N, Jackson G, Gardner-Medwin J (2003) Biologic therapies for juvenile arthritis. Arch Dis Child 88(3):186–191PubMedCrossRef
10.
go back to reference Gartlehner G, Hansen RA, Jonas BL et al (2006) The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: A systematic review and metaanalysis. J Rheumatol 33(12):2398–2408PubMed Gartlehner G, Hansen RA, Jonas BL et al (2006) The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: A systematic review and metaanalysis. J Rheumatol 33(12):2398–2408PubMed
11.
go back to reference Lovell DJ (2004) Preliminary data from a study of adalimumab in children with JIA. Arthritis Rheum 50:S436 (Suppl) Lovell DJ (2004) Preliminary data from a study of adalimumab in children with JIA. Arthritis Rheum 50:S436 (Suppl)
12.
go back to reference Irigoyen PI, Olson J, Hom C (2004) Treatment of systemic onset juvenile rheumatoid arthritis with anakinra. Arthritis Rheum 50:S437 (Suppl) Irigoyen PI, Olson J, Hom C (2004) Treatment of systemic onset juvenile rheumatoid arthritis with anakinra. Arthritis Rheum 50:S437 (Suppl)
13.
14.
go back to reference Lovell DJ, Ruperto N, Cuttica R (2004) Randomized trial of infliximab plus methotrexate for the treatment of polyarticular juvenile rheumatoid arthritis poster. American College of Rheumatology 68th Annual Scientific Meeting. San Antonio, TX Lovell DJ, Ruperto N, Cuttica R (2004) Randomized trial of infliximab plus methotrexate for the treatment of polyarticular juvenile rheumatoid arthritis poster. American College of Rheumatology 68th Annual Scientific Meeting. San Antonio, TX
15.
go back to reference Gartlehner G, Hansen RA, Thieda P et al (2005) Drug class review on targeted immune modulators. Drug Effectiveness Review Project, Portland Gartlehner G, Hansen RA, Thieda P et al (2005) Drug class review on targeted immune modulators. Drug Effectiveness Review Project, Portland
16.
go back to reference Fox DM (2005) Evidence of evidence-based health policy: the politics of systematic reviews in coverage decisions. Health Aff (Millwood) 24(1):114–122CrossRef Fox DM (2005) Evidence of evidence-based health policy: the politics of systematic reviews in coverage decisions. Health Aff (Millwood) 24(1):114–122CrossRef
17.
go back to reference Giannini EH, Ruperto N, Ravelli A et al (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40(7):1202–1209PubMed Giannini EH, Ruperto N, Ravelli A et al (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40(7):1202–1209PubMed
18.
go back to reference Giannini EH, Lovell DJ, Felson DT et al (1994) Preliminary core set of outcome variables for use in JRA clinical trials. Arthritis Rheum 37:S428 (Suppl)CrossRef Giannini EH, Lovell DJ, Felson DT et al (1994) Preliminary core set of outcome variables for use in JRA clinical trials. Arthritis Rheum 37:S428 (Suppl)CrossRef
19.
go back to reference Harris RP, Helfand M, Woolf SH et al (2001) Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 20(3):21–35PubMedCrossRef Harris RP, Helfand M, Woolf SH et al (2001) Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 20(3):21–35PubMedCrossRef
20.
go back to reference Anonymous (2001) Undertaking systematic reviews of research on effectiveness: CRD’s guidance for those carrying out or commissioning reviews. CRD report number 4, 2nd edn. CRD, York Anonymous (2001) Undertaking systematic reviews of research on effectiveness: CRD’s guidance for those carrying out or commissioning reviews. CRD report number 4, 2nd edn. CRD, York
21.
go back to reference Deeks JJ, Dinnes J, D’Amico R et al (2003) Evaluating non-randomised intervention studies. Health Technol Assess 7(27):iii–x, 1–173PubMed Deeks JJ, Dinnes J, D’Amico R et al (2003) Evaluating non-randomised intervention studies. Health Technol Assess 7(27):iii–x, 1–173PubMed
23.
go back to reference Ruperto N (2006) 2006 EULAR meeting proceedings. 48-week data from the study of adalimumab in children with juvenile rheumatoid arthritis (JR). Ann Rheum Dis 65:OP0007 (Suppl) Ruperto N (2006) 2006 EULAR meeting proceedings. 48-week data from the study of adalimumab in children with juvenile rheumatoid arthritis (JR). Ann Rheum Dis 65:OP0007 (Suppl)
24.
go back to reference Andrias R, Porras O, Rudge S (2002) Preliminary data from a study of kineret (anakinra) in children with juvenile rheumatoid arthritis abstract. Arthritis Rheum 46:496 (Suppl) Andrias R, Porras O, Rudge S (2002) Preliminary data from a study of kineret (anakinra) in children with juvenile rheumatoid arthritis abstract. Arthritis Rheum 46:496 (Suppl)
25.
go back to reference Ilowite NT, Reiff A, Rudge S et al (2006) Abstract 723: A randomized, multi-center, blinded, placebo-controlled study with an open-label run-in period to evaluate anakinra in polyarticular-course juvenile rheumatoid arthritis. American College of Rheumatology National Scientific Meeting Ilowite NT, Reiff A, Rudge S et al (2006) Abstract 723: A randomized, multi-center, blinded, placebo-controlled study with an open-label run-in period to evaluate anakinra in polyarticular-course juvenile rheumatoid arthritis. American College of Rheumatology National Scientific Meeting
26.
go back to reference Lovell DJ, Giannini EH, Reiff A et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 342(11):763–769PubMedCrossRef Lovell DJ, Giannini EH, Reiff A et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 342(11):763–769PubMedCrossRef
27.
go back to reference Horneff G, Schmeling H, Biedermann T et al (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 63(12):1638–1644PubMedCrossRef Horneff G, Schmeling H, Biedermann T et al (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 63(12):1638–1644PubMedCrossRef
28.
go back to reference Henrickson M, Reiff A (2004) Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 31(10):2055–2061PubMed Henrickson M, Reiff A (2004) Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 31(10):2055–2061PubMed
29.
go back to reference Kietz DA, Pepmueller PH, Moore TL (2002) Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period. Ann Rheum Dis 61(2):171–173PubMedCrossRef Kietz DA, Pepmueller PH, Moore TL (2002) Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period. Ann Rheum Dis 61(2):171–173PubMedCrossRef
30.
go back to reference Quartier P, Taupin P, Bourdeaut F et al (2003) Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 48(4):1093–1101PubMedCrossRef Quartier P, Taupin P, Bourdeaut F et al (2003) Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 48(4):1093–1101PubMedCrossRef
31.
go back to reference Russo RA, Katsicas MM, Zelazko M (2002) Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 20(5):723–726PubMed Russo RA, Katsicas MM, Zelazko M (2002) Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 20(5):723–726PubMed
32.
go back to reference Lahdenne P, Vahasalo P, Honkanen V (2003) Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis 62(3):245–247PubMedCrossRef Lahdenne P, Vahasalo P, Honkanen V (2003) Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis 62(3):245–247PubMedCrossRef
34.
go back to reference Lovell DJ, Giannini EH, Reiff A et al (2003) Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: Interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum 48(1):218–226PubMedCrossRef Lovell DJ, Giannini EH, Reiff A et al (2003) Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: Interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum 48(1):218–226PubMedCrossRef
35.
go back to reference Lovell DJ, Reiff A, Jones OY et al (2006) Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 54(6):1987–1994PubMedCrossRef Lovell DJ, Reiff A, Jones OY et al (2006) Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 54(6):1987–1994PubMedCrossRef
36.
go back to reference Tauber T, Turetz J, Barash J et al (2006) Optic neuritis associated with etanercept therapy for juvenile arthritis. J AAPOS 10(1):26–29PubMedCrossRef Tauber T, Turetz J, Barash J et al (2006) Optic neuritis associated with etanercept therapy for juvenile arthritis. J AAPOS 10(1):26–29PubMedCrossRef
37.
go back to reference Gerloni V, Pontikaki I, Gattinara M et al (2005) Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum 52(2):548–553PubMedCrossRef Gerloni V, Pontikaki I, Gattinara M et al (2005) Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum 52(2):548–553PubMedCrossRef
38.
go back to reference Katsicas MM, Russo RA (2005) Use of infliximab in patients with systemic juvenile idiopathic arthritis refractory to etanercept. Clin Exp Rheumatol 23(4):545–548PubMed Katsicas MM, Russo RA (2005) Use of infliximab in patients with systemic juvenile idiopathic arthritis refractory to etanercept. Clin Exp Rheumatol 23(4):545–548PubMed
39.
go back to reference Masatlioglu S, Gogus F, Cevrigen D (2002) Infliximab in the treatment of refractory juvenile idiopathic arthritis. Arthritis Rheum 46(9):S481 Masatlioglu S, Gogus F, Cevrigen D (2002) Infliximab in the treatment of refractory juvenile idiopathic arthritis. Arthritis Rheum 46(9):S481
40.
go back to reference Scarazatti M, Beltramelli M, Dell’Era L (2001) Infliximab in juvenile idiopathis arthrits abstract. Ann Rheum Dis 60:ii17–ii53 (abstract P180) Scarazatti M, Beltramelli M, Dell’Era L (2001) Infliximab in juvenile idiopathis arthrits abstract. Ann Rheum Dis 60:ii17–ii53 (abstract P180)
41.
go back to reference Honkanen V, Tynjala P, Vahasalo P (2002) Infliximab in juvenile arthritis: 1-year follow up abstract. Arthritis Rheum 46:1272 (Suppl) Honkanen V, Tynjala P, Vahasalo P (2002) Infliximab in juvenile arthritis: 1-year follow up abstract. Arthritis Rheum 46:1272 (Suppl)
42.
go back to reference Woo P, Wilkinson N, Prieur AM et al (2005) Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 7(6):R1281–R1288PubMedCrossRef Woo P, Wilkinson N, Prieur AM et al (2005) Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 7(6):R1281–R1288PubMedCrossRef
43.
go back to reference Yokota S, Miyamae T, Imagawa T et al (2005) Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 52(3):818–825PubMedCrossRef Yokota S, Miyamae T, Imagawa T et al (2005) Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 52(3):818–825PubMedCrossRef
44.
go back to reference Yokota S, Imagawa T, Mori M et al (2006) Abstract 722: Rapid improvement of signs and symptoms associated with systemic juvenile idiopathic arthritis (sJIA) by interleukin-6 (IL-6) blockade—results from a tocilizumab sJIA phase III clinical trial. American College of Rheumatology National Scientific Meetings Yokota S, Imagawa T, Mori M et al (2006) Abstract 722: Rapid improvement of signs and symptoms associated with systemic juvenile idiopathic arthritis (sJIA) by interleukin-6 (IL-6) blockade—results from a tocilizumab sJIA phase III clinical trial. American College of Rheumatology National Scientific Meetings
45.
go back to reference Genovese MC, Bathon JM, Martin RW et al (2002) Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 46(6):1443–1450PubMedCrossRef Genovese MC, Bathon JM, Martin RW et al (2002) Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 46(6):1443–1450PubMedCrossRef
46.
go back to reference Higgins G, Jones K, Rennebohm R (2000) Variable response of systemic juvenile rheumatoid arthritis to etanercept abstract. Arthritis Rheum 43:S257 (Suppl) Higgins G, Jones K, Rennebohm R (2000) Variable response of systemic juvenile rheumatoid arthritis to etanercept abstract. Arthritis Rheum 43:S257 (Suppl)
47.
go back to reference Kimura Y, Pinho P, Walco G et al (2005) Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 32(5):935–942PubMed Kimura Y, Pinho P, Walco G et al (2005) Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 32(5):935–942PubMed
48.
go back to reference Kietz DA, Pepmueller PH, Moore TL (2001) Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis. J Rheumatol 28(2):360–362PubMed Kietz DA, Pepmueller PH, Moore TL (2001) Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis. J Rheumatol 28(2):360–362PubMed
49.
go back to reference Haapasaari J, Kautiainen H, Hannula S et al (2002) Good results from combining etanercept to prevailing DMARD therapy in refractory juvenile idiopathic arthritis. Clin Exp Rheumatol 20(6):867–870PubMed Haapasaari J, Kautiainen H, Hannula S et al (2002) Good results from combining etanercept to prevailing DMARD therapy in refractory juvenile idiopathic arthritis. Clin Exp Rheumatol 20(6):867–870PubMed
50.
go back to reference Schmeling H, Mathony K, John V et al (2001) A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: A pilot study. Ann Rheum Dis 60(4):410–412PubMedCrossRef Schmeling H, Mathony K, John V et al (2001) A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: A pilot study. Ann Rheum Dis 60(4):410–412PubMedCrossRef
Metadata
Title
Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence
Authors
Gerald Gartlehner
Richard A. Hansen
Beth L. Jonas
Patricia Thieda
Kathleen N. Lohr
Publication date
01-01-2008
Publisher
Springer-Verlag
Published in
Clinical Rheumatology / Issue 1/2008
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-007-0654-6

Other articles of this Issue 1/2008

Clinical Rheumatology 1/2008 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.