Targeted therapy for systemic sclerosis: how close are we?
Despite recent etiopathogenetic advances, systemic sclerosis continues to be one of the most complex systemic autoimmune disease in terms of its therapeutic management. There is no drug tested for any autoimmune disease that has not also been tested for systemic sclerosis, but none have proven effective. Substantial changes have occurred in the last decade, however, with the appearance of new therapeutic targets and the consequent development of highly selective drugs, some of which, such as endothelin antagonists, are now widely used and others, such as tyrosine kinase inhibitors, in which much hope has been placed. There is also increasing interest in evaluating drugs that are capable of blocking fibrotic processes mediated by transforming growth factor beta, which are currently used in nonautoimmune diseases (such as antidiabetic drugs or statins). Unfortunately, recent trials on these new molecules have produced negative results. Increasing research into disease-specific therapies targeting distinct biological pathways should continue. In the future, it is hoped that the simultaneous or sequential use of different drugs will provide better results than currently available monotherapies in patients with systemic sclerosis.
Ramos-Casals
Manuel
M
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain. mramos@clinic.ub.es
Fonollosa-Pla
Vicent
V
Brito-Zerón
Pilar
P
Sisó-Almirall
Antoni
A
D015415:Biomarkers / Q000097:blood; D016503:Drug Delivery Systems; D016232:Endothelins / Q000037:antagonists & inhibitors; D005355:Fibrosis / Q000503:physiopathology; D006801:Humans; D011379:Prognosis; D012595:Scleroderma, Systemic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy
D015415:Biomarkers; D016232:Endothelins
Eur J Clin Invest. 2006 Sep;36 Suppl 3:10-5
16919005
Clin Exp Rheumatol. 2001 Sep-Oct;19(5):503-8
11579708
J Rheumatol. 2005 Nov;32(11):2164-6
16265695
Arthritis Rheum. 2004 Dec;50(12):3985-93
15593188
Ann Intern Med. 2000 Jun 6;132(11):871-9
10836913
J Clin Invest. 1987 Jun;79(6):1665-73
3034979
Clin Exp Rheumatol. 2007 Jan-Feb;25(1):23-8
17417986
Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v8-9
18784153
Reumatismo. 2007 Apr-Jun;59(2):135-9
17603693
Chest. 2008 Feb;133(2):455-60
18071023
J Rheumatol. 2009 Oct;36(10):2264-8
19755613
Arthritis Rheum. 2009 Apr;60(4):1102-11
19333948
Nat Rev Rheumatol. 2009 Jun;5(6):300-2
19491908
Rheumatology (Oxford). 2009 Jan;48(1):49-52
18815156
N Engl J Med. 2005 Nov 24;353(21):2229-42
16306520
Ann Intern Med. 1994 Feb 1;120(3):199-206
7506013
N Engl J Med. 2006 Jun 22;354(25):2667-76
16790699
J Rheumatol. 2009 Jul;36(7):1550-2
19567637
Arthritis Rheum. 2009 May;60(5):1519-29
19404935
Arthritis Res Ther. 2009;11(2):R30
19261182
Chest. 2008 Jul;134(1):152-7
18628217
Br J Rheumatol. 1996 Apr;35(4):364-72
8624641
Nat Clin Pract Rheumatol. 2006 Mar;2(3):134-44
16932673
Rheumatology (Oxford). 2008 Apr;47(4):464-6
18263597
Arthritis Rheum. 2009 Apr;60(4):1137-44
19333949
Lancet. 2007 Jul 28;370(9584):342-50
17662883
Clin Exp Rheumatol. 2007 Mar-Apr;25(2):287-92
17543155
Am J Respir Crit Care Med. 2005 May 1;171(9):1040-7
15665326
Circulation. 2002 Sep 17;106(12):1477-82
12234951
Intern Med. 2002 Dec;41(12):1118-23
12521199
Medicine (Baltimore). 2007 Jul;86(4):242-251
17632266
Respir Med. 2008 Jan;102(1):150-5
17822892
Nat Med. 2006 Aug;12(8):908-16
16862153
Lancet. 2008 Jun 21;371(9630):2093-100
18572079
Am J Respir Crit Care Med. 2005 Nov 1;172(9):1228-9; author reply 1229
16249322
Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v5-7
18784145
Ann Rheum Dis. 2009 May;68(5):620-8
19147617
Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii1-2
19487216
J Biol Regul Homeost Agents. 2009 Jan-Mar;23(1):23-9
19321043
J Rheumatol. 2008 Sep;35(9):1801-8
18709692
Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v12-3
18784127
J Rheumatol. 2002 Feb;29(2):298-304
11842824
Eur Respir J. 2004 Sep;24(3):353-9
15358690
Eur Respir J. 2002 May;19(5):906-11
12030732
Rheumatology (Oxford). 2004 Nov;43(11):1454-6
15502001
Intern Med. 2008;47(6):511-3
18344637
Eur Respir J. 2007 Aug;30(2):338-44
17504794
J Rheumatol. 2007 Dec;34(12):2417-22
17985403
Am J Pathol. 2009 Feb;174(2):519-33
19147827
J Clin Pharmacol. 2009 Nov;49(11):1343-52
19755415
Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii35-8
19022811
Chest. 2004 Aug;126(2):420-7
15302727
Open Respir Med J. 2008;2:39-45
19340324
Lancet. 2001 Oct 6;358(9288):1119-23
11597664
Am J Med Sci. 2009 May;337(5):329-35
19295413
J Heart Lung Transplant. 2007 Jan;26(1):63-9
17234519
Ann Rheum Dis. 2007 Nov;66(11):1467-72
17472992
Arthritis Rheum. 2006 Jun;54(6):1946-51
16729283
Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31
19487219
Arthritis Rheum. 2001 Jun;44(6):1351-8
11407694
Rheumatology (Oxford). 2008 May;47(5):735-7
18326532
J Rheumatol. 2008 Jul;35(7):1323-8
18528965
Rheumatology (Oxford). 2009 Jan;48(1):61-4
19022831
Heart. 2006 Jul;92(7):926-32
16339813
Lancet. 2006 May 20;367(9523):1683-91
16714190
Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v2-4
18784131
J Pathol. 2009 Mar;217(4):534-42
19086038
Circulation. 2005 Nov 8;112(19):2980-5
16275885
Am J Respir Crit Care Med. 2006 Dec 1;174(11):1257-63
16946127
Arthritis Rheum. 2006 Dec;54(12):3962-70
17133610
Arthritis Res Ther. 2008;10(5):R124
18937831
N Engl J Med. 2002 Mar 21;346(12):896-903
11907289
Nat Rev Rheumatol. 2009 Apr;5(4):200-6
19337284
Nat Rev Rheumatol. 2009 Jul;5(7):357-8
19568247
BMJ. 1989 Mar 4;298(6673):561-4
2467711
Blood. 2007 Aug 15;110(4):1388-96
17452515
Ann Rheum Dis. 2005 Sep;64(9):1387
16100356
Arthritis Rheum. 2009 Feb;60(2):578-83
19180481
J Dermatol Sci. 1995 Jan;9(1):45-7
7537081
J Rheumatol. 2008 Jun;35(6):1064-72
18464307
Adv Exp Med Biol. 2007;612:88-103
18161483
Arthritis Rheum. 2009 Jul;60(7):2142-55
19565505
Arthritis Rheum. 2006 Jan;54(1):192-201
16385515
Ann Rheum Dis. 2009 Sep;68(9):1433-9
18782794
Nat Clin Pract Rheumatol. 2008 Apr;4(4):184-91
18285764
Arthritis Rheum. 2007 Jan;56(1):323-33
17195236
Ann Rheum Dis. 2008 Jan;67(1):98-104
17526554
Circulation. 2009 Jun 9;119(22):2894-903
19470885
J Am Coll Cardiol. 2006 May 16;47(10):2049-56
16697324
Rheumatol Int. 2007 Feb;27(4):357-61
17021713
Am J Respir Crit Care Med. 2008 Jan 1;177(1):75-81
17901413
Arthritis Rheum. 2008 Aug;58(8):2549-52
18668570
Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii49-53
19487225
N Engl J Med. 2009 May 7;360(19):1989-2003
19420368
Am J Nephrol. 2005 Nov-Dec;25(6):611-20
16308546
Nat Clin Pract Rheumatol. 2009 Feb;5(2):70-1
19182811
Arthritis Rheum. 2009 Jan;60(1):219-24
19116940
Ann Rheum Dis. 2010 Jan;69(1):193-7
19103636
Ann Intern Med. 2008 Oct 21;149(8):521-30
18936500
J Invest Dermatol. 2005 Oct;125(4):692-9
16185267
FASEB J. 2008 Jul;22(7):2214-22
18326784
Clin Rheumatol. 2009 Dec;28(12):1379-84
19690939
Arthritis Rheum. 2007 Jan;56(1):311-22
17195235
Rheumatol Int. 2009 May;29(7):769-75
19037604
Clin Exp Rheumatol. 2007 Mar-Apr;25(2):293-6
17543156
Arthritis Rheum. 2009 Feb;60(2):584-91
19180499
J Clin Invest. 2009 May;119(5):1066-73
19411764
N Engl J Med. 2006 Jun 15;354(24):2531-41
16775234
Presse Med. 2006 Apr;35(4 Pt 1):587-92
16614599
Arthritis Rheum. 2008 Aug;58(8):2528-37
18668566
N Engl J Med. 2005 Nov 17;353(20):2148-57
16291984
Arthritis Rheum. 2003 May;48(5):1190-9
12746891
Eur Respir J. 2006 Dec;28(6):1195-203
16899485
Ann Rheum Dis. 2007 Oct;66(10):1398-9
17881663
N Engl J Med. 2002 Aug 1;347(5):322-9
12151469
Am J Respir Crit Care Med. 2004 Feb 15;169(4):441-7
14630619
N Engl J Med. 2006 Jun 15;354(24):2542-51
16775235
Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34
17717203
J Am Coll Cardiol. 2002 Aug 21;40(4):780-8
12204511
Ann Intern Med. 2000 Mar 21;132(6):425-34
10733441