title: Targeted therapy for systemic sclerosis: how close are we?
abstract: 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.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain. mramos@clinic.ub.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos-Casals
authors.forename: Vicent
authors.initials: V
authors.lastname: Fonollosa-Pla
authors.forename: Pilar
authors.initials: P
authors.lastname: Brito-Zerón
authors.forename: Antoni
authors.initials: A
authors.lastname: Sisó-Almirall
mesh_terms: 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
chemical_list: D015415:Biomarkers; D016232:Endothelins
references.citation: Eur J Clin Invest. 2006 Sep;36 Suppl 3:10-5
references.pmid: 16919005
references.citation: Clin Exp Rheumatol. 2001 Sep-Oct;19(5):503-8
references.pmid: 11579708
references.citation: J Rheumatol. 2005 Nov;32(11):2164-6
references.pmid: 16265695
references.citation: Arthritis Rheum. 2004 Dec;50(12):3985-93
references.pmid: 15593188
references.citation: Ann Intern Med. 2000 Jun 6;132(11):871-9
references.pmid: 10836913
references.citation: J Clin Invest. 1987 Jun;79(6):1665-73
references.pmid: 3034979
references.citation: Clin Exp Rheumatol. 2007 Jan-Feb;25(1):23-8
references.pmid: 17417986
references.citation: Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v8-9
references.pmid: 18784153
references.citation: Reumatismo. 2007 Apr-Jun;59(2):135-9
references.pmid: 17603693
references.citation: Chest. 2008 Feb;133(2):455-60
references.pmid: 18071023
references.citation: J Rheumatol. 2009 Oct;36(10):2264-8
references.pmid: 19755613
references.citation: Arthritis Rheum. 2009 Apr;60(4):1102-11
references.pmid: 19333948
references.citation: Nat Rev Rheumatol. 2009 Jun;5(6):300-2
references.pmid: 19491908
references.citation: Rheumatology (Oxford). 2009 Jan;48(1):49-52
references.pmid: 18815156
references.citation: N Engl J Med. 2005 Nov 24;353(21):2229-42
references.pmid: 16306520
references.citation: Ann Intern Med. 1994 Feb 1;120(3):199-206
references.pmid: 7506013
references.citation: N Engl J Med. 2006 Jun 22;354(25):2667-76
references.pmid: 16790699
references.citation: J Rheumatol. 2009 Jul;36(7):1550-2
references.pmid: 19567637
references.citation: Arthritis Rheum. 2009 May;60(5):1519-29
references.pmid: 19404935
references.citation: Arthritis Res Ther. 2009;11(2):R30
references.pmid: 19261182
references.citation: Chest. 2008 Jul;134(1):152-7
references.pmid: 18628217
references.citation: Br J Rheumatol. 1996 Apr;35(4):364-72
references.pmid: 8624641
references.citation: Nat Clin Pract Rheumatol. 2006 Mar;2(3):134-44
references.pmid: 16932673
references.citation: Rheumatology (Oxford). 2008 Apr;47(4):464-6
references.pmid: 18263597
references.citation: Arthritis Rheum. 2009 Apr;60(4):1137-44
references.pmid: 19333949
references.citation: Lancet. 2007 Jul 28;370(9584):342-50
references.pmid: 17662883
references.citation: Clin Exp Rheumatol. 2007 Mar-Apr;25(2):287-92
references.pmid: 17543155
references.citation: Am J Respir Crit Care Med. 2005 May 1;171(9):1040-7
references.pmid: 15665326
references.citation: Circulation. 2002 Sep 17;106(12):1477-82
references.pmid: 12234951
references.citation: Intern Med. 2002 Dec;41(12):1118-23
references.pmid: 12521199
references.citation: Medicine (Baltimore). 2007 Jul;86(4):242-251
references.pmid: 17632266
references.citation: Respir Med. 2008 Jan;102(1):150-5
references.pmid: 17822892
references.citation: Nat Med. 2006 Aug;12(8):908-16
references.pmid: 16862153
references.citation: Lancet. 2008 Jun 21;371(9630):2093-100
references.pmid: 18572079
references.citation: Am J Respir Crit Care Med. 2005 Nov 1;172(9):1228-9; author reply 1229
references.pmid: 16249322
references.citation: Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v5-7
references.pmid: 18784145
references.citation: Ann Rheum Dis. 2009 May;68(5):620-8
references.pmid: 19147617
references.citation: Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii1-2
references.pmid: 19487216
references.citation: J Biol Regul Homeost Agents. 2009 Jan-Mar;23(1):23-9
references.pmid: 19321043
references.citation: J Rheumatol. 2008 Sep;35(9):1801-8
references.pmid: 18709692
references.citation: Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v12-3
references.pmid: 18784127
references.citation: J Rheumatol. 2002 Feb;29(2):298-304
references.pmid: 11842824
references.citation: Eur Respir J. 2004 Sep;24(3):353-9
references.pmid: 15358690
references.citation: Eur Respir J. 2002 May;19(5):906-11
references.pmid: 12030732
references.citation: Rheumatology (Oxford). 2004 Nov;43(11):1454-6
references.pmid: 15502001
references.citation: Intern Med. 2008;47(6):511-3
references.pmid: 18344637
references.citation: Eur Respir J. 2007 Aug;30(2):338-44
references.pmid: 17504794
references.citation: J Rheumatol. 2007 Dec;34(12):2417-22
references.pmid: 17985403
references.citation: Am J Pathol. 2009 Feb;174(2):519-33
references.pmid: 19147827
references.citation: J Clin Pharmacol. 2009 Nov;49(11):1343-52
references.pmid: 19755415
references.citation: Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii35-8
references.pmid: 19022811
references.citation: Chest. 2004 Aug;126(2):420-7
references.pmid: 15302727
references.citation: Open Respir Med J. 2008;2:39-45
references.pmid: 19340324
references.citation: Lancet. 2001 Oct 6;358(9288):1119-23
references.pmid: 11597664
references.citation: Am J Med Sci. 2009 May;337(5):329-35
references.pmid: 19295413
references.citation: J Heart Lung Transplant. 2007 Jan;26(1):63-9
references.pmid: 17234519
references.citation: Ann Rheum Dis. 2007 Nov;66(11):1467-72
references.pmid: 17472992
references.citation: Arthritis Rheum. 2006 Jun;54(6):1946-51
references.pmid: 16729283
references.citation: Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31
references.pmid: 19487219
references.citation: Arthritis Rheum. 2001 Jun;44(6):1351-8
references.pmid: 11407694
references.citation: Rheumatology (Oxford). 2008 May;47(5):735-7
references.pmid: 18326532
references.citation: J Rheumatol. 2008 Jul;35(7):1323-8
references.pmid: 18528965
references.citation: Rheumatology (Oxford). 2009 Jan;48(1):61-4
references.pmid: 19022831
references.citation: Heart. 2006 Jul;92(7):926-32
references.pmid: 16339813
references.citation: Lancet. 2006 May 20;367(9523):1683-91
references.pmid: 16714190
references.citation: Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v2-4
references.pmid: 18784131
references.citation: J Pathol. 2009 Mar;217(4):534-42
references.pmid: 19086038
references.citation: Circulation. 2005 Nov 8;112(19):2980-5
references.pmid: 16275885
references.citation: Am J Respir Crit Care Med. 2006 Dec 1;174(11):1257-63
references.pmid: 16946127
references.citation: Arthritis Rheum. 2006 Dec;54(12):3962-70
references.pmid: 17133610
references.citation: Arthritis Res Ther. 2008;10(5):R124
references.pmid: 18937831
references.citation: N Engl J Med. 2002 Mar 21;346(12):896-903
references.pmid: 11907289
references.citation: Nat Rev Rheumatol. 2009 Apr;5(4):200-6
references.pmid: 19337284
references.citation: Nat Rev Rheumatol. 2009 Jul;5(7):357-8
references.pmid: 19568247
references.citation: BMJ. 1989 Mar 4;298(6673):561-4
references.pmid: 2467711
references.citation: Blood. 2007 Aug 15;110(4):1388-96
references.pmid: 17452515
references.citation: Ann Rheum Dis. 2005 Sep;64(9):1387
references.pmid: 16100356
references.citation: Arthritis Rheum. 2009 Feb;60(2):578-83
references.pmid: 19180481
references.citation: J Dermatol Sci. 1995 Jan;9(1):45-7
references.pmid: 7537081
references.citation: J Rheumatol. 2008 Jun;35(6):1064-72
references.pmid: 18464307
references.citation: Adv Exp Med Biol. 2007;612:88-103
references.pmid: 18161483
references.citation: Arthritis Rheum. 2009 Jul;60(7):2142-55
references.pmid: 19565505
references.citation: Arthritis Rheum. 2006 Jan;54(1):192-201
references.pmid: 16385515
references.citation: Ann Rheum Dis. 2009 Sep;68(9):1433-9
references.pmid: 18782794
references.citation: Nat Clin Pract Rheumatol. 2008 Apr;4(4):184-91
references.pmid: 18285764
references.citation: Arthritis Rheum. 2007 Jan;56(1):323-33
references.pmid: 17195236
references.citation: Ann Rheum Dis. 2008 Jan;67(1):98-104
references.pmid: 17526554
references.citation: Circulation. 2009 Jun 9;119(22):2894-903
references.pmid: 19470885
references.citation: J Am Coll Cardiol. 2006 May 16;47(10):2049-56
references.pmid: 16697324
references.citation: Rheumatol Int. 2007 Feb;27(4):357-61
references.pmid: 17021713
references.citation: Am J Respir Crit Care Med. 2008 Jan 1;177(1):75-81
references.pmid: 17901413
references.citation: Arthritis Rheum. 2008 Aug;58(8):2549-52
references.pmid: 18668570
references.citation: Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii49-53
references.pmid: 19487225
references.citation: N Engl J Med. 2009 May 7;360(19):1989-2003
references.pmid: 19420368
references.citation: Am J Nephrol. 2005 Nov-Dec;25(6):611-20
references.pmid: 16308546
references.citation: Nat Clin Pract Rheumatol. 2009 Feb;5(2):70-1
references.pmid: 19182811
references.citation: Arthritis Rheum. 2009 Jan;60(1):219-24
references.pmid: 19116940
references.citation: Ann Rheum Dis. 2010 Jan;69(1):193-7
references.pmid: 19103636
references.citation: Ann Intern Med. 2008 Oct 21;149(8):521-30
references.pmid: 18936500
references.citation: J Invest Dermatol. 2005 Oct;125(4):692-9
references.pmid: 16185267
references.citation: FASEB J. 2008 Jul;22(7):2214-22
references.pmid: 18326784
references.citation: Clin Rheumatol. 2009 Dec;28(12):1379-84
references.pmid: 19690939
references.citation: Arthritis Rheum. 2007 Jan;56(1):311-22
references.pmid: 17195235
references.citation: Rheumatol Int. 2009 May;29(7):769-75
references.pmid: 19037604
references.citation: Clin Exp Rheumatol. 2007 Mar-Apr;25(2):293-6
references.pmid: 17543156
references.citation: Arthritis Rheum. 2009 Feb;60(2):584-91
references.pmid: 19180499
references.citation: J Clin Invest. 2009 May;119(5):1066-73
references.pmid: 19411764
references.citation: N Engl J Med. 2006 Jun 15;354(24):2531-41
references.pmid: 16775234
references.citation: Presse Med. 2006 Apr;35(4 Pt 1):587-92
references.pmid: 16614599
references.citation: Arthritis Rheum. 2008 Aug;58(8):2528-37
references.pmid: 18668566
references.citation: N Engl J Med. 2005 Nov 17;353(20):2148-57
references.pmid: 16291984
references.citation: Arthritis Rheum. 2003 May;48(5):1190-9
references.pmid: 12746891
references.citation: Eur Respir J. 2006 Dec;28(6):1195-203
references.pmid: 16899485
references.citation: Ann Rheum Dis. 2007 Oct;66(10):1398-9
references.pmid: 17881663
references.citation: N Engl J Med. 2002 Aug 1;347(5):322-9
references.pmid: 12151469
references.citation: Am J Respir Crit Care Med. 2004 Feb 15;169(4):441-7
references.pmid: 14630619
references.citation: N Engl J Med. 2006 Jun 15;354(24):2542-51
references.pmid: 16775235
references.citation: Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34
references.pmid: 17717203
references.citation: J Am Coll Cardiol. 2002 Aug 21;40(4):780-8
references.pmid: 12204511
references.citation: Ann Intern Med. 2000 Mar 21;132(6):425-34
references.pmid: 10733441