title: The safety profile of biologic therapies for juvenile idiopathic arthritis.
abstract: The treatment of juvenile idiopathic arthritis (JIA) has been revolutionized by the use of novel biologic agents that have much improved patients' short-term and, according to early evidence, long-term outcomes. Currently available biologic agents used to treat patients with JIA include tumor necrosis factor (TNF) blockers, various agents that target interleukin (IL)-1 and the IL-6 receptor, T-cell co-stimulation inhibitors and antibodies to B-lymphocyte antigen CD20. These agents are increasingly used early in the course of the disease (often in combination with other immunosuppressive medications) and often for long periods of time, as patients can be difficult to wean from their use. Safety concerns (especially the long-term effects of biologic therapy) are, therefore, being examined more closely. For instance, in 2009, the FDA issued a warning related to the development of malignancies in patients with JIA who had used anti-TNF medications for >2.5 years. In this Review, data related to the safety profile of all currently available biologic agents used to treat JIA are examined, with a particular focus on anti-TNF therapy, the most studied biologic agent for JIA. Safety issues that need further study, including the implementation of registries to monitor long-term drug safety, are also discussed.
authors.affiliation: Pediatric Rheumatology Unit, Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem 91031, Israel. hashkesp@szmc.org.il
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hashkes
authors.forename: Yosef
authors.initials: Y
authors.lastname: Uziel
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Laxer
mesh_terms: D000293:Adolescent; D016907:Adverse Drug Reaction Reporting Systems; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001691:Biological Therapy / Q000009:adverse effects*; D002648:Child; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
references.citation: Rheumatol Int. 2010 Apr;30(6):801-4
references.pmid: 19506877
references.citation: Clin Exp Rheumatol. 2007 Jan-Feb;25(1):119
references.pmid: 17418007
references.citation: Ann Rheum Dis. 2003 Mar;62(3):245-7
references.pmid: 12594111
references.citation: Arthritis Rheum. 2003 Apr;48(4):1093-101
references.pmid: 12687553
references.citation: Ann Rheum Dis. 2010 Apr;69(4):718-22
references.pmid: 20237125
references.citation: Pediatr Clin North Am. 1995 Oct;42(5):1099-125
references.pmid: 7567188
references.citation: JAMA. 2005 Oct 5;294(13):1671-84
references.pmid: 16204667
references.citation: Ann Rheum Dis. 2009 Apr;68(4):519-25
references.pmid: 18413440
references.citation: Biologics. 2009;3:127-39
references.pmid: 19707402
references.citation: J Rheumatol. 2007 Dec;34(12):2503-4
references.pmid: 18061971
references.citation: J Clin Rheumatol. 2008 Oct;14(5):297-8
references.pmid: 18824922
references.citation: J AAPOS. 2006 Feb;10(1):26-9
references.pmid: 16527676
references.citation: Arthritis Rheum. 2010 Jun;62(6):1792-802
references.pmid: 20191582
references.citation: Ann Rheum Dis. 2009 Apr;68(4):552-7
references.pmid: 18467515
references.citation: Am J Ophthalmol. 2009 Nov;148(5):696-703.e1
references.pmid: 19664754
references.citation: Rheumatol Int. 2007 Dec;28(2):153-6
references.pmid: 17641897
references.citation: Rheumatology (Oxford). 2004 Apr;43(4):527-9
references.pmid: 15024141
references.citation: Arthritis Rheum. 2010 Aug;62(8):2517-24
references.pmid: 20506368
references.citation: N Engl J Med. 2008 Aug 21;359(8):810-20
references.pmid: 18716298
references.citation: Arthritis Rheum. 2013 Sep;65(9):2486-96
references.pmid: 23754188
references.citation: J Rheumatol. 2008 Aug;35(8):1681
references.pmid: 18671329
references.citation: J Clin Rheumatol. 2009 Jun;15(4):161-4
references.pmid: 19363453
references.citation: Arthritis Rheum. 2005 Feb 15;53(1):18-23
references.pmid: 15696578
references.citation: J Rheumatol. 2001 Jul;28(7):1677-80
references.pmid: 11469478
references.citation: Arthritis Rheum. 2001 Dec;44(12):2862-9
references.pmid: 11762947
references.citation: Ann Rheum Dis. 2009 Dec;68(12):1863-9
references.pmid: 19147611
references.citation: Biologics. 2008 Dec;2(4):865-74
references.pmid: 19707464
references.citation: Arthritis Rheum. 2010 Feb;62(2):599-608
references.pmid: 20112378
references.citation: J Rheumatol. 2008 Aug;35(8):1680-1
references.pmid: 18671328
references.citation: Arthritis Rheum. 2000 Nov;43(11):2606-8
references.pmid: 11083287
references.citation: J Rheumatol Suppl. 1992 Apr;33:6-10
references.pmid: 1593604
references.citation: Arthritis Rheum. 2002 Oct;46(10):2565-70
references.pmid: 12384912
references.citation: Arthritis Care Res (Hoboken). 2010 Nov;62(11):1542-51
references.pmid: 20597110
references.citation: Cytokine. 2008 Jun;42(3):293-7
references.pmid: 18445529
references.citation: Arthritis Rheum. 2006 Jun;54(6):1987-94
references.pmid: 16732547
references.citation: Arthritis Rheum. 2003 Jan;48(1):218-26
references.pmid: 12528122
references.citation: Ann Rheum Dis. 2008 Aug;67(8):1145-52
references.pmid: 17981916
references.citation: Arthritis Rheum. 2008 Jun 15;59(6):762-84
references.pmid: 18512708
references.citation: Ann Rheum Dis. 2004 Dec;63(12):1638-44
references.pmid: 15115709
references.citation: Clin Exp Rheumatol. 2003 Sep-Oct;21(5):645-6
references.pmid: 14611117
references.citation: Clin Exp Rheumatol. 2003 Mar-Apr;21(2):276-7
references.pmid: 12747299
references.citation: Ann Rheum Dis. 2009 May;68(5):635-41
references.pmid: 18413443
references.citation: Ann Rheum Dis. 2009 Jul;68(7):1228-9
references.pmid: 19525408
references.citation: J Rheumatol. 2003 Feb;30(2):401-3
references.pmid: 12563702
references.citation: Rheumatology (Oxford). 2009 Aug;48(8):916-9
references.pmid: 19483091
references.citation: Rheumatol Int. 2008 Aug;28(10):1031-4
references.pmid: 18369626
references.citation: Acta Reumatol Port. 2007 Apr-Jun;32(2):139-50
references.pmid: 17572652
references.citation: Arthritis Rheum. 2007 Sep;56(9):3096-106
references.pmid: 17763439
references.citation: N Engl J Med. 2000 Mar 16;342(11):763-9
references.pmid: 10717011
references.citation: Ann Rheum Dis. 2009 Apr;68(4):607-8
references.pmid: 19286909
references.citation: J Rheumatol. 2005 May;32(5):935-42
references.pmid: 15868633
references.citation: Lancet. 2008 Aug 2;372(9636):383-91
references.pmid: 18632147
references.citation: Rheum Dis Clin North Am. 1991 Nov;17(4):891-905
references.pmid: 1767079
references.citation: Rheumatology (Oxford). 2009 Apr;48(4):445-6
references.pmid: 19164423
references.citation: J Pediatr. 2006 Dec;149(6):833-6
references.pmid: 17137902
references.citation: Arthritis Res Ther. 2005;7(6):R1281-8
references.pmid: 16277681
references.citation: Lancet. 2008 Mar 22;371(9617):998-1006
references.pmid: 18358927
references.citation: Rheumatology (Oxford). 2006 Nov;45(11):1448-9
references.pmid: 16920752
references.citation: Ann Rheum Dis. 2006 Sep;65(9):1259
references.pmid: 16905590
references.citation: Rheumatology (Oxford). 2002 Dec;41(12):1450-2
references.pmid: 12468829
references.citation: Arthritis Rheum. 2008 May;58(5):1496-504
references.pmid: 18438876
references.citation: J Pediatr Gastroenterol Nutr. 2004 Aug;39(2):203-6
references.pmid: 15269630
references.citation: Ann Rheum Dis. 2008 Mar;67(3):302-8
references.pmid: 17947302
references.citation: Clin Rheumatol. 2009 Feb;28(2):129-37
references.pmid: 18766426
references.citation: Arthritis Rheum. 2009 Sep;60(9):2794-804
references.pmid: 19714630