Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the adult and pediatric experiences.
Biologics have advanced the therapy of adult and pediatric arthritis. They have been linked to rare serious adverse outcomes, but the actual risk of these events is controversial in adults, and largely unknown in pediatrics. Because of the paucity of safety and efficacy data in children, pediatric rheumatologists often rely on the adult literature. Herein, we reviewed the adult and pediatric literature on five classes of medicines: Tumor necrosis factor (TNF) inhibitors, anakinra, rituximab, abatacept, and tocilizumab. For efficacy, we reviewed randomized controlled studies in adults, but did include lesser qualities of evidence for pediatrics. For safety, we utilized prospective and retrospective studies, rarely including reports from other inflammatory conditions. The review included studies on rheumatoid arthritis and spondyloarthritis, as well as juvenile idiopathic arthritis. Overall, we found that the TNF inhibitors have generally been found safe and effective in adult and pediatric use, although risks of infections and other adverse events are discussed. Anakinra, rituximab, abatacept, and tocilizumab have also shown positive results in adult trials, but there is minimal pediatric data published with the exception of small studies involving the subgroup of children with systemic onset juvenile idiopathic arthritis, in whom anakinra and tocilizumab may be effective therapies.
Stoll
Matthew L
ML
Department of Pediatrics, Division of Rheumatology, UT Southwestern Medical Center, Dallas, TX, USA.
Gotte
Alisa C
AC
Arthritis Rheum. 2003 Nov;48(11):3202-6
14613283
J Rheumatol. 2004 Feb;31(2):390-2
14760812
Arthritis Rheum. 2001 Jun;44(6):1411-5
11407702
Arthritis Rheum. 2007 May;56(5):1433-9
17469100
Best Pract Res Clin Rheumatol. 2004 Feb;18(1):59-80
15123038
Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii62-3
12379625
Ann Rheum Dis. 2006 Dec;65(12):1572-7
16968715
Ann Rheum Dis. 2006 Mar;65(3):316-20
16096329
Arthritis Rheum. 2006 Jul;54(7):2136-46
16802350
Ann Rheum Dis. 2007 Feb;66(2):143-50
17068064
Arthritis Res Ther. 2005;7 Suppl 3:S19-25
15960818
Ann Rheum Dis. 2005 Oct;64(10):1414-20
15843454
Clin Exp Rheumatol. 1997 May-Jun;15 Suppl 17:S27-38
9266130
Arthritis Res Ther. 2004;6(6):R535-43
15535831
Arthritis Rheum. 2007 Sep;56(9):2896-904
17763441
FDA Consum. 2007 Mar-Apr;41(2):3
17582852
Allergol Immunopathol (Madr). 2007 Mar-Apr;35(2):52-6
17428400
Ann Rheum Dis. 2006 May;65(5):617-22
16249224
Neurology. 2001 Nov 27;57(10):1885-8
11723281
J Rheumatol. 2007 Feb;34(2):430-3
17295433
Ann Rheum Dis. 2004 May;63(5):508-16
15082480
Arthritis Rheum. 1996 Jul;39(7):1092-101
8670316
Rheumatol Int. 2007 Dec;28(2):153-6
17641897
Rheumatology (Oxford). 2004 Apr;43(4):527-9
15024141
J Rheumatol. 2007 May;34(5):1040-50
17444593
J Clin Rheumatol. 2007 Aug;13(4):219-20
17762459
Ann Rheum Dis. 2006 Sep;65(9):1255-7
16540545
J Pediatr. 2006 May;148(5):623-627
16737873
Arthritis Rheum. 2007 May;56(5):1417-23
17469098
Dermatology. 2006;213(3):182-6
17033165
Lancet. 2008 Mar 22;371(9617):987-97
18358926
Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666-70
1103152
Clin Exp Rheumatol. 2007 Jan-Feb;25(1):119
17418007
Arthritis Rheum. 2006 Dec;54(12):3782-9
17133559
Ann Rheum Dis. 2005 Jun;64(6):913-20
15550531
J Exp Med. 2005 May 2;201(9):1479-86
15851489
J Rheumatol. 2005 Nov;32(11):2109-15
16265687
Bull NYU Hosp Jt Dis. 2006;64(1-2):72-6
17121494
N Engl J Med. 1999 Jan 28;340(4):253-9
9920948
Arthritis Rheum. 2005 Feb;52(2):548-53
15693004
J Rheumatol. 2007 May;34(5):1146-50
17343318
J Rheumatol. 2002 May;29(5):869-74
12022342
Ann Rheum Dis. 2003 Mar;62(3):245-7
12594111
Ann Rheum Dis. 2007 Feb;66(2):228-34
16935912
Lancet. 2000 Jul 29;356(9227):385-90
10972371
Ann Rheum Dis. 2005 May;64(5):699-703
15695534
Arthritis Rheum. 2005 Oct;52(10):3279-89
16200601
Semin Arthritis Rheum. 2007 Dec;37(3):189-97
17583775
Mt Sinai J Med. 2005 Jul;72(4):250-6
16021319
Am J Med Sci. 2007 Mar;333(3):137-9
17496730
Arthritis Rheum. 2005 Feb 15;53(1):18-23
15696578
Ann Rheum Dis. 2005 Jul;64(7):1098-9
15958773
Ann Rheum Dis. 2007 Mar;66(3):422-3
17179171
Ann Rheum Dis. 2005 Aug;64(8):1150-7
15677701
J Pediatr. 2007 Apr;150(4):376-82
17382113
Medicine (Baltimore). 2007 Jul;86(4):242-251
17632266
Scand J Rheumatol. 2000;29(3):160-2
10898067
Arthritis Rheum. 2003 Jan;48(1):35-45
12528101
Br J Rheumatol. 1995 Apr;34(4):334-42
7788147
Arthritis Rheum. 2004 Feb;50(2):353-63
14872476
Arthritis Rheum. 2005 Aug;52(8):2263-71
16052582
J Pediatr. 2006 Oct;149(4):572-5
17011337
Clin Exp Rheumatol. 2002 Sep-Oct;20(5 Suppl 27):S21-5
14989425
J Rheumatol. 2004 Oct;31(10):2071-5
15468378
Arthritis Rheum. 2006 Apr;54(4):1075-86
16572442
Ann Rheum Dis. 2004 Sep;63(9):1062-8
15082469
Int J Hematol. 2006 Jul;84(1):48-53
16867902
Arthritis Rheum. 2003 Apr;48(4):1093-101
12687553
Arthritis Rheum. 1998 Sep;41(9):1552-63
9751087
Arthritis Rheum. 2003 Jun;48(6):1667-75
12794835
Arthritis Rheum. 2004 May;50(5):1400-11
15146409
Mod Rheumatol. 2007;17(3):191-7
17564773
Br J Rheumatol. 1995 May;34(5):454-60
7788176
Arthritis Rheum. 2006 Aug;54(8):2368-76
16868999
Ann Rheum Dis. 2007 Jun;66(6):842-3
17513574
Clin Rheumatol. 2008 Jan;27(1):67-76
17570009
Arthritis Rheum. 2002 Sep;46(9):2287-93
12355475
Arthritis Rheum. 2006 Jun;54(6):1987-94
16732547
Arthritis Rheum. 2006 Jul;54(7):2314-20
16802372
Blood. 1996 Mar 15;87(6):2095-147
8630372
Curr Opin Pharmacol. 2004 Aug;4(4):314-20
15251122
Ann Intern Med. 1999 Mar 16;130(6):478-86
10075615
Arthritis Rheum. 2002 Mar;46(3):614-24
11920396
J Rheumatol. 2007 Feb;34(2):380-5
17013997
N Engl J Med. 1997 Jul 17;337(3):141-7
9219699
Ann Rheum Dis. 2004 Dec;63(12):1638-44
15115709
Arthritis Rheum. 2005 Jun;52(6):1794-803
15934079
Arthritis Rheum. 2006 Mar;54(3):692-701
16508929
Clin Rheumatol. 2006 Nov;25(6):929-33
16328088
J Pediatr. 2005 Feb;146(2):217-21
15689912
Rheumatology (Oxford). 2006 Aug;45(8):982-9
16461435
Br J Rheumatol. 1997 May;36(5):589-93
9189062
Clin Rheumatol. 2007 Dec;26(12):2173-2175
17579802
Ann Rheum Dis. 2005 Nov;64(11):1568-75
15829577
Arthritis Res Ther. 2006;8(4):R131
16869978
Clin Rheumatol. 1998;17(5):359-63
9805178
N Engl J Med. 2003 Feb 13;348(7):601-8
12584368
Nature. 1990 Jan 25;343(6256):341-6
2137201
Arthritis Rheum. 2004 Apr;50(4):1107-16
15077292
Blood. 2006 Apr 1;107(7):2639-42
16352811
JAMA. 2006 May 17;295(19):2275-85
16705109
Ann Rheum Dis. 2007 Mar;66(3):419-21
16901959
Pediatrics. 1969 Jul;44(1):92-100
4978557
Bone Marrow Transplant. 2004 Aug;34(3):241-7
15235579
J Rheumatol. 2002 Jul;29(7):1520-30
12136914
Pediatr Blood Cancer. 2008 Apr;50(4):822-5
17570702
Blood. 2002 Aug 1;100(3):1104-5
12150156
Clin Exp Rheumatol. 2003 Mar-Apr;21(2):276-7
12747299
Arthritis Rheum. 2002 Dec;46(12):3143-50
12483717
Arthritis Rheum. 2005 Jul;52(7):2103-8
15986366
Arthritis Rheum. 2007 Jun;56(6):1754-64
17530704
J Rheumatol. 2006 Jan;33(1):37-44
16395748
Arthritis Rheum. 2007 Aug;56(8):2715-8
17665440
Arthritis Rheum. 1991 Sep;34(9):1158-63
1930333
Ophthalmology. 2006 May;113(5):860-4.e2
16545455
Arthritis Rheum. 2005 Oct;52(10):3168-74
16200620
Ann Rheum Dis. 2007 Apr;66(4):548-50
17068061
Arthritis Rheum. 2002 Dec;46(12):3151-8
12483718
Curr Opin Rheumatol. 2006 Sep;18(5):507-11
16896291
Rheum Dis Clin North Am. 2004 May;30(2):365-80, vii
15172046
J Rheumatol. 2005 Apr;32(4):740-3
15801034
Curr Opin Rheumatol. 2007 May;19(3):308-13
17414961
Arthritis Rheum. 2003 Apr;48(4):927-34
12687534
J Clin Pharmacol. 2005 May;45(5):490-7
15831771
Clin Exp Rheumatol. 2002 Sep-Oct;20(5):723-6
12412209
Arthritis Rheum. 2005 Nov;52(11):3403-12
16255017
Arthritis Res Ther. 2005;7(3):R545-51
15899041
Arthritis Rheum. 2003 Nov;48(11):3230-6
14613288
N Engl J Med. 2005 Sep 15;353(11):1114-23
16162882
Arthritis Rheum. 2007 Sep;56(9):2815-6
17763434
J Rheumatol. 2007 Apr;34(4):892-3
17407250
Rheumatology (Oxford). 2005 Aug;44(8):1008-11
15855187
Arthritis Rheum. 2006 Sep;54(9):2757-64
16947774
Transplantation. 2003 Jul 27;76(2):435-6
12883208
Arthritis Rheum. 1998 Dec;41(12):2196-204
9870876
Clin Exp Rheumatol. 2005 Jul-Aug;23(4):545-8
16095128
Rheumatol Int. 2007 Nov;28(1):47-9
17564711
Ann Rheum Dis. 2007 May;66(5):704-5
17324973
Ann Rheum Dis. 2005 Oct;64(10):1421-6
15829572
Ann Rheum Dis. 2003 Dec;62(12):1168-77
14644854
J Rheumatol. 2002 May;29(5):1111-4
12022340
Curr Rheumatol Rep. 2006 Dec;8(6):450-8
17092444
Thorax. 2005 Oct;60(10):800-5
16055611
Arthritis Rheum. 2006 Sep;54(9):2817-29
16947782
Arthritis Rheum. 2005 Jun;52(6):1766-72
15934089
Arthritis Rheum. 2005 Apr;52(4):1227-36
15818699
Arthritis Rheum. 2004 Jun;50(6):1740-51
15188349
Arthritis Rheum. 2006 Sep;54(9):2807-16
16947384
Scand J Rheumatol. 2004;33(2):82-6
15163108
Arthritis Rheum. 2005 Feb;52(2):582-91
15692973
J Rheumatol. 2007 Jul;34(7):1590-2
17610313
Arthritis Rheum. 2006 Feb 15;55(1):163-6
16463396
Ann Rheum Dis. 2005 Apr;64(4):647-8
15374853
Lancet. 2001 Nov 3;358(9292):1511-3
11705566
Reumatismo. 2007 Jan-Mar;59(1):50-6
17435842
Arthritis Rheum. 2005 Mar;52(3):818-25
15751095
Arthritis Rheum. 2005 Jan;52(1):239-46
15641089
Arthritis Rheum. 2004 Jan;50(1):277-90
14730626
Arthritis Rheum. 2004 May;50(5):1412-9
15146410
Cancer Res. 1993 Feb 15;53(4):851-6
8428365
Rheumatology (Oxford). 2007 Jun;46(6):980-2
17384180
Postgrad Med J. 2004 Jan;80(939):26
14760175
Ann Rheum Dis. 2003 Aug;62(8):791
12860745
N Engl J Med. 2004 Jun 17;350(25):2572-81
15201414
J Rheumatol. 2006 Apr;33(4):722-31
16583475
Clin Exp Ophthalmol. 2005 Oct;33(5):461-8
16181269
J Exp Med. 2007 Sep 3;204(9):2131-44
17724127
Leuk Res. 2006 Mar;30 Suppl 1:S16-21
16750674
Arthritis Rheum. 2000 Dec;43(12):2648-59
11145022
Rheumatology (Oxford). 2006 Sep;45(9):1129-32
16522678
Mod Rheumatol. 2012 Feb;22(1):109-15
21667343
Immunity. 2006 Mar;24(3):233-8
16546089
Arthritis Rheum. 2002 Mar;46(3):755-65
11920412
Ophthalmology. 2006 Feb;113(2):308-14
16406545
Rheumatology (Oxford). 2007 Jul;46(7):1157-60
17478469
Arthritis Rheum. 2004 Nov;50(11):3432-43
15529377
Nat Clin Pract Rheumatol. 2007 Apr;3(4):227-33
17396108
Clin Exp Immunol. 1988 Jul;73(1):88-92
2458872
Ann Rheum Dis. 2005 May;64(5):657-8
15834052
Ann Rheum Dis. 2007 Sep;66(9):1162-7
17485422
Cancer Treat Rev. 2005 Oct;31(6):456-73
16054760
Arthritis Rheum. 2007 Sep;56(9):3096-106
17763439
N Engl J Med. 2000 Mar 16;342(11):763-9
10717011
Int J Immunopharmacol. 1992 Apr;14(3):475-80
1535616
Int J Clin Pract. 2007 Mar;61(3):494-500
17313619
Arthritis Rheum. 2005 Sep;52(9):2740-50
16142737
Blood. 2002 Feb 15;99(4):1486-8
11830505
Arthritis Rheum. 2006 Feb;54(2):628-34
16447241
Arthritis Rheum. 2006 Jan;54(1):26-37
16385520
Arthritis Rheum. 2006 Sep;54(9):2793-806
16947627
Lancet. 2004 Feb 28;363(9410):675-81
15001324
J Rheumatol. 2005 May;32(5):935-42
15868633
Annu Rev Immunol. 2001;19:225-52
11244036
J Clin Invest. 1999 May;103(9):1243-52
10225967
Ann Rheum Dis. 2002 Oct;61(10):883-8
12228157
Arthritis Rheum. 2006 May;54(5):1390-400
16649186
Rheumatol Int. 2004 May;24(3):173-6
14648110
Arthritis Rheum. 2000 May;43(5):1001-9
10817552
J Rheumatol. 2000 Apr;27(4):841-50
10782805
Ann Rheum Dis. 2004 Dec;63(12):1594-600
15345498
Ann Rheum Dis. 2006 Aug;65(8):1006-12
16396977
Dig Dis Sci. 2007 Jun;52(6):1481-4
17429728
Lancet. 1994 Oct 22;344(8930):1105-10
7934491
J Rheumatol Suppl. 2005 Mar;74:8-12
15742458
Arthritis Res Ther. 2006;8(5):111
16911768
N Engl J Med. 2003 Nov 13;349(20):1907-15
14614165
J Rheumatol. 2004 Oct;31(10):2055-61
15468375
J Rheumatol. 2001 Nov;28(11):2544-7
11708431
J Rheumatol. 2003 Dec;30(12):2563-71
14719195
Br J Ophthalmol. 2007 Mar;91(3):319-24
17035274
Rheumatology (Oxford). 2003 May;42(5):617-21
12709536
J Formos Med Assoc. 2004 Aug;103(8):618-23
15340661
Arthritis Rheum. 2006 Nov;54(11):3399-407
17075823
Arthritis Rheum. 2007 Sep;56(9):2886-95
17729297
Ann Intern Med. 2006 Jun 20;144(12):865-76
16785475
Cell Mol Life Sci. 2000 Sep;57(10):1457-70
11078023
J Exp Med. 1991 Sep 1;174(3):561-9
1714933
Arthritis Res Ther. 2005;7(6):R1281-8
16277681
Lancet. 2008 Mar 22;371(9617):998-1006
18358927
Expert Opin Drug Saf. 2005 May;4(3):599-608
15934864
Arthritis Rheum. 2003 Aug;48(8):2122-7
12905464
Arthritis Rheum. 2005 Jan;52(1):27-35
15641102
Rheumatology (Oxford). 2006 Nov;45(11):1448-9
16920752
Ann Rheum Dis. 2006 Sep;65(9):1259
16905590
Arthritis Rheum. 2007 Apr;56(4):1125-33
17393394
Arthritis Rheum. 2007 Jun;56(6):1954-65
17530721
Arthritis Rheum. 2006 Feb;54(2):613-20
16447239
J Rheumatol. 2000 Sep;27(9):2256-63
10990244
J Rheumatol. 2004 Sep;31(9):1876
15338480
Semin Oncol. 1999 Oct;26(5 Suppl 14):66-73
10561020
Arthritis Rheum. 2002 Jun;46(6):1470-9
12115176
Clin Infect Dis. 2006 Nov 15;43(10):e95-100
17051484
Clin Exp Rheumatol. 2006 Jan-Feb;24(1):65-9
16539821
J Clin Invest. 1998 Oct 1;102(7):1369-76
9769329
Joint Bone Spine. 2006 Dec;73(6):710-3
17127088
Clin Neuropathol. 2007 Mar-Apr;26(2):68-73
17416105
Ann Rheum Dis. 2002 Oct;61(10):941-2
12228171
Rheumatology (Oxford). 2007 Feb;46(2):327-34
16880188
Clin Exp Rheumatol. 1999 Nov-Dec;17(6 Suppl 18):S121-4
10589370
Clin Rheumatol. 2007 Nov;26(11):1969-71
17340045
Rheumatology (Oxford). 2007 Apr;46(4):626-30
17189244
Arthritis Rheum. 2004 Jun;50(6):1761-9
15188351
Aliment Pharmacol Ther. 2003 Jan;17(1):75-84
12492735
Ann Rheum Dis. 2002 Feb;61(2):171-3
11796406
Ann Rheum Dis. 2007 Oct;66(10):1339-44
17261532
Ann Rheum Dis. 2008 Mar;67(3):302-8
17947302
N Engl J Med. 2000 Nov 30;343(22):1594-602
11096166
J Rheumatol. 2006 Dec;33(12):2398-408
17225293