Abatacept in difficult-to-treat juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade.
Kuemmerle-Deschner
Jasmin B
JB
Pediatric Rheumatology Clinics, Dept of Pediatrics, University Hospital Tübingen, Germany;
Benseler
Sm
S
J Rheumatol. 2004 Feb;31(2):390-2
14760812
J Immunol. 2004 May 15;172(10):6435-43
15128835
Rheumatology (Oxford). 2007 Feb;46(2):308-13
16877460
J Rheumatol Suppl. 1992 Apr;33:6-10
1593604
J Rheumatol. 2002 May;29(5):1058-64
12022323
Rheumatol Int. 2005 Apr;25(3):169-78
15688190
Curr Rheumatol Rep. 2006 Dec;8(6):450-8
17092444
Arthritis Rheum. 2006 Sep;54(9):2807-16
16947384
Arthritis Rheum. 2005 Mar;52(3):818-25
15751095
Science. 1994 Aug 26;265(5176):1225-7
7520604
Arthritis Rheum. 2007 Nov;56(11):3793-804
17968951
Arthritis Rheum. 2002 Oct;46(10):2721-9
12384932
J Immunol. 1998 Sep 15;161(6):2762-71
9743334
Ann Rheum Dis. 2008 Apr;67(4):547-54
17921185
Pediatrics. 2002 Jan;109(1):109-15
11773549
Lancet. 2007 Mar 3;369(9563):767-778
17336654
Ann Rheum Dis. 2007 Feb;66(2):228-34
16935912
Pediatr Clin North Am. 1995 Oct;42(5):1099-125
7567188
Nat Clin Pract Rheumatol. 2007 Jul;3(7):382-90
17599072
Nat Rev Drug Discov. 2003 Jun;2(6):473-88
12776222
Arthritis Res Ther. 2005;7(2):R241-9
15743470
JAMA. 2005 Oct 5;294(13):1671-84
16204667
J Exp Med. 1999 Mar 15;189(6):969-78
10075980
Arthritis Rheum. 2003 May;48(5):1398-407
12746913
Eur J Immunol. 1996 Oct;26(10):2320-8
8898940
Arch Dis Child. 2003 Mar;88(3):186-91
12598373
J Rheumatol. 2005 May;32(5):935-42
15868633
J Clin Invest. 1999 May;103(9):1243-52
10225967
Clin Exp Rheumatol. 1999 May-Jun;17(3):367-74
10410275
Z Rheumatol. 2008 Mar;67(2):111-6, 118-20
18309499
Arthritis Rheum. 2004 Sep;50(9):2920-30
15457461
Lancet. 2008 Aug 2;372(9636):383-91
18632147
Rheum Dis Clin North Am. 1991 Nov;17(4):891-905
1767079
N Engl J Med. 2003 Nov 13;349(20):1907-15
14614165
Arthritis Res Ther. 2005;7(6):R1281-8
16277681
Ann Intern Med. 2006 Jun 20;144(12):865-76
16785475
Arthritis Res Ther. 2005;7(2):R256-67
15743472
J Exp Med. 1993 Nov 1;178(5):1801-6
8228826
N Engl J Med. 2005 Apr 21;352(16):1655-66
15843668
Ann Rheum Dis. 2006 Oct;65(10):1351-6
16504994
J Rheumatol. 2000 Sep;27(9):2256-63
10990244
Arthritis Rheum. 2002 Jun;46(6):1470-9
12115176
J Clin Invest. 1998 Oct 1;102(7):1369-76
9769329
Ann Rheum Dis. 2008 Mar;67(3):302-8
17947302
J Endocrinol. 2007 Jun;193(3):323-30
17535871
J Rheumatol. 2006 Dec;33(12):2398-408
17225293