Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: Lessons from clinical trials

Current Rheumatology Reports

Volumn 11, Issue 2, 2009, Pages 111-119

  Tashkin, Donald P ^a   Au, Karen ^b   Khanna, Dinesh ^b   Clements, Philip J ^b   Furst, Daniel E ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

AZATHIOPRINE; BOSENTAN; CELL ADHESION MOLECULE; CHLORAMBUCIL; CONNECTIVE TISSUE GROWTH FACTOR; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DASATINIB; ENDOTHELIN 1; IMATINIB; INTERLEUKIN 10; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 6; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PENICILLAMINE; PLACEBO; PLATELET DERIVED GROWTH FACTOR; PREDNISONE; THROMBIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; VASCULOTROPIN; ANTIRHEUMATIC AGENT; BLOCKING ANTIBODY; DRUG DERIVATIVE; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 13; MONOCLONAL ANTIBODY; MYCOPHENOLIC ACID; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; THIAZOLE DERIVATIVE;

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DISEASE FREE SURVIVAL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DYSPNEA; ENDOTHELIUM INJURY; FORCED EXPIRATORY VOLUME; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMORRHAGIC CYSTITIS; HIGH RESOLUTION COMPUTER TOMOGRAPHY; HUMAN; INTERSTITIAL LUNG DISEASE; LOW DRUG DOSE; LUNG ALVEOLITIS; LUNG FUNCTION; LUNG FUNCTION TEST; LUNG LAVAGE; MORTALITY; OBSERVATIONAL STUDY; PATHOGENESIS; PHYSICAL CAPACITY; PREDICTION; RANDOMIZED CONTROLLED TRIAL; REVIEW; SURVIVAL RATE; SYSTEMIC SCLEROSIS; TOTAL LUNG CAPACITY; TREATMENT DURATION; TREATMENT OUTCOME; IMMUNOLOGY; PATHOPHYSIOLOGY;

ANTIBODIES, BLOCKING; ANTIBODIES, MONOCLONAL; ANTIRHEUMATIC AGENTS; CYCLOPHOSPHAMIDE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERLEUKIN-13; LUNG DISEASES, INTERSTITIAL; MYCOPHENOLIC ACID; PIPERAZINES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESPIRATORY FUNCTION TESTS; SCLERODERMA, SYSTEMIC; THIAZOLES; TREATMENT OUTCOME;

EID: 65549124538     PISSN: 15233774     EISSN: 15346307     Source Type: Journal    
DOI: 10.1007/s11926-009-0016-2     Document Type: Review

References (62)

1. V.D. Steen T.A. Medsger Jr 2007 Changes in causes of death in systemic sclerosis Ann Rheum Dis 66 940 944 17329309 10.1136/ard.2006.066068 (Pubitemid 46999798)
2. M. Beon R.A. Harley A. Wessels, et al. 2004 Myofibroblast induction and microvascular alteration in scleroderma lung fibrosis Clin Exp Rheumatol 22 733 742 15638048 1:STN:280:DC%2BD2M%2Fht1GisA%3D%3D
3. E. Scala S. Pallotta A. Frezzolini, et al. 2004 Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement Clin Exp Immunol 138 540 546 15544634 10.1111/j.1365-2249.2004. 02642.x 1:CAS:528:DC%2BD2cXhtFGms7zJ (Pubitemid 39573637)
4. G.S. Bogatkevich E. Gustilo J.C. Oates, et al. 2005 Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts Am J Physiol Lung Cell Mol Physiol 288 L190 L201 15447940 10.1152/ajplung.00448.2003 1:CAS:528:DC%2BD2MXhtVGitrk%3D (Pubitemid 40023901)
5. X. Shi-Wen Y. Chen C.P. Denton, et al. 2004 Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts Mol Biol Cell 15 2707 2719 15047866 10.1091/mbc.E03-12-0902 (Pubitemid 38691860)
6. D.J. Abraham R. Vancheeswaran M.R. Dashwood, et al. 1997 Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease Am J Pathol 151 831 841 9284832 1:STN:280:ByiH3s%2Fnt1E%3D
7. A. Leask 2008 Targeting the TGF-beta, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma Cell Signal 20 1409 1414 18296024 10.1016/j.cellsig.2008.01.006 1:CAS:528:DC%2BD1cXnsFKkur4%3D
8. T. Krieg D. Abraham R. Lafyatis 2007 Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions Arthritis Res Ther 9 Suppl2 S4 17767742 10.1186/ar2188
9. D. Bouros A.U. Wells A.G. Nicholson, et al. 2002 Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome Am J Respir Crit Care Med 165 1581 1586 12070056 10.1164/rccm.2106012 (Pubitemid 34693935)
10. V.D. Steen C. Conte G.R. Owens T.A. Medsger Jr. 1994 Severe restrictive lung disease in systemic sclerosis Arthritis Rheum 37 1283 1289 7945490 10.1002/art.1780370903 1:STN:280:ByqD3s3itl0%3D (Pubitemid 24320744)
11. C. Strange M.B. Bolster M.D. Roth, et al. 2008 Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease Am J Respir Crit Care Med 177 91 98 17901414 10.1164/rccm.200705-655OC 1:CAS:528:DC%2BD1cXht12mt7k%3D
12. P.I. Latsi R.M. du Bois A.G. Nicholson, et al. 2003 Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends Am J Respir Crit Care Med 168 531 537 12791580 10.1164/rccm.200210-1245OC (Pubitemid 37088594)
13. J.G. Goldin D.A. Lynch D.C. Strollo, et al. 2008 High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease Chest 134 358 367 18641099 10.1378/chest.07-2444
14. N.S. Goh S.R. Desai S. Veeraraghavan, et al. 2008 Interstitial lung disease in systemic sclerosis: a simple staging system Am J Respir Crit Care Med 177 1248 1254 18369202 10.1164/rccm.200706-877OC (Pubitemid 351860934)
15. V.D. Steen T.A. Medsger Jr G.P. Rodnan 1982 D-penicillamine therapy in progressive systemic sclerosis (scleroderma): a retrospective analysis Ann Intern Med 97 652 659 7137731 1:STN:280:DyaL3s%2Fks1Kitg%3D%3D
16. P.J. Clements D.E. Furst W.K. Wong, et al. 1999 High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial Arthritis Rheum 42 1194 1203 10366112 10.1002/1529-0131(199906)42:6<1194::AID-ANR16>3.0.CO;2-7 1:CAS:528:DyaK1MXktVegtLw%3D (Pubitemid 29268956)
17. D.E. Furst P.J. Clements S. Hillis, et al. 1989 Immunosuppression with chlorambucil, versus placebo, for scleroderma. Results of a three-year, parallel, randomized, double-blind study Arthritis Rheum 32 584 593 2655606 10.1002/anr.1780320512 1:STN:280:BiaB2cnmtFE%3D (Pubitemid 19146699)
18. American Thoracic Society 2000 Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med 161 646 664
19. J.P. Lynch III R. Saggar S.S. Weigt, et al. 2006 Usual interstitial pneumonia Semin Respir Crit Care Med 27 634 651 17195140 10.1055/s-2006-957335 (Pubitemid 46048043)
20. R.M. Silver J.H. Warrick M.B. Kinsella, et al. 1993 Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease J Rheumatol 20 838 844 8336309 1:STN:280:ByyA38bmslI%3D
21. V.D. Steen J.K. Lanz Jr C. Conte, et al. 1994 Therapy for severe interstitial lung disease in systemic sclerosis. A retrospective study Arthritis Rheum 37 1290 1296 7945491 10.1002/art.1780370904 1:STN:280:ByqD3s3isVQ%3D (Pubitemid 24320745)
22. B. White W.C. Moore F.M. Wigley, et al. 2000 Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis Ann Intern Med 132 947 954 10858177 1:CAS:528:DC%2BD3cXkslylsb8%3D
23. A. Akesson A. Scheja A. Lundin F.A. Wollheim 1994 Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide Arthritis Rheum 37 729 735 8185701 10.1002/art.1780370518 1:STN:280:ByuB2c3ht1M%3D
24. J. Behr C. Vogelmeier T. Beinert, et al. 1996 Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung Am J Respir Crit Care Med 154 400 406 8756813 1:STN:280:BymA38fhtlY%3D
25. A. Schnabel M. Reuter W.L. Gross 1998 Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease due to collagen vascular diseases Arthritis Rheum 41 1215 1220 9663478 10.1002/1529-0131(199807)41:7<1215::AID- ART11>3.0.CO;2-Y 1:CAS:528:DyaK1cXkslWjtLo%3D (Pubitemid 28313423)
26. G. Varai L. Earle S.A. Jimenez, et al. 1998 A pilot study of intermittent intravenous cyclophosphamide for the treatment of systemic sclerosis associated lung disease J Rheumatol 25 1325 1329 9676764 1:CAS:528:DyaK1cXkslWjsLw%3D
27. I. Pakas J.P. Ioannidis K. Malagari, et al. 2002 Cyclophosphamide with low or high dose prednisolone for systemic sclerosis lung disease J Rheumatol 29 298 304 11842824 1:CAS:528:DC%2BD38XhsF2iu78%3D
28. R. Giacomelli G. Valentini F. Salsano, et al. 2002 Cyclophosphamide pulse regimen in the treatment of alveolitis in systemic sclerosis J Rheumatol 29 731 736 11950014 1:CAS:528:DC%2BD38XjtFGltLw%3D
29. B. Griffiths S. Miles H. Moss, et al. 2002 Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function J Rheumatol 29 2371 2378 12415594 1:CAS:528:DC%2BD38XptVGgt7s%3D
30. D.P. Tashkin R. Elashoff P.J. Clements, et al. 2006 Cyclophosphamide versus placebo in scleroderma lung disease N Engl J Med 354 2655 2666 16790698 10.1056/NEJMoa055120 1:CAS:528:DC%2BD28XmtFSgtLs%3D (Pubitemid 43920839)
31. D. Khanna X. Yan D.P. Tashkin, et al. 2007 Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study Arthritis Rheum 56 1676 1684 17469162 10.1002/art.22580 1:CAS:528:DC%2BD2sXmsFartb4%3D (Pubitemid 46764099)
32. J.G. Goldin D.A. Lynch D.C. Strollo, et al. 2008 Follow-up HRCT after treatment of scleroderma-interstitial lung disease with cyclophosphamide demonstrates evidence for treatment effect [abstract] Am J Respir Crit Care Med 177 A882
33. F.J. Martinez W.J. McCune 2006 Cyclophosphamide for scleroderma lung disease N Engl J Med 354 2707 2709 16790705 10.1056/NEJMe068095 1:CAS:528:DC%2BD28XmtFSgsb0%3D (Pubitemid 43920846)
34. D.P. Tashkin R. Elashoff P.J. Clements, et al. 2007 Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease Am J Respir Crit Care Med 176 1026 1034 17717203 10.1164/rccm.200702- 326OC 1:CAS:528:DC%2BD2sXhsVekt7%2FN (Pubitemid 350127847)
35. R.K. Hoyles R.W. Ellis J. Wellsbury, et al. 2006 A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma Arthritis Rheum 54 3962 3970 17133610 10.1002/art.22204 1:CAS:528:DC%2BD2sXktlalug%3D%3D (Pubitemid 44955900)
36. N. Takebe X. Cheng T.E. Fandy, et al. 2006 IMP dehydrogenase inhibitor mycophenolate mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells Mol Cancer Ther 5 457 466 16505121 10.1158/1535-7163.MCT-05-0340 1:CAS:528:DC%2BD28XhvVelsbs%3D
37. M. Colic Z. Stojic-Vukanic B. Pavlovic, et al. 2003 Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells Clin Exp Immunol 134 63 69 12974756 10.1046/j.1365-2249.2003.02269.x 1:CAS:528:DC%2BD3sXos1Cks78%3D (Pubitemid 37186589)
38. E. Andrikos A. Yavuz V. Bordoni, et al. 2005 Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line Transplant Proc 37 3226 3229 16213354 10.1016/j.transproceed.2005.07.001 1:CAS:528:DC%2BD2MXhtVyntbvN (Pubitemid 41435667)
39. D. Kaminska B. Tyran O. Mazanowska, et al. 2005 Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs tacrolimus) influences the intragraft mRNA expression of cytokines in human kidney allograft biopsies by in situ RTPCR analysis Transplant Proc 37 770 772 15848526 10.1016/j.transproceed.2004.12.144 1:CAS:528:DC%2BD2MXjsFKjtL8%3D (Pubitemid 40590695)
40. S.N. Liossis A. Bounas A.P. Andonopoulos 2006 Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease Rheumatology (Oxford) 45 1005 1008 10.1093/rheumatology/kei211 1:CAS:528:DC%2BD28Xotl2ku7w%3D (Pubitemid 44283057)
41. S.I. Nihtyanova G.M. Brough C.M. Black C.P. Denton 2007 Mycophenolate mofetil in diffuse cutaneous systemic sclerosis-a retrospective analysis Rheumatology (Oxford) 46 442 445 10.1093/rheumatology/kel244 1:CAS:528:DC%2BD2sXhvFWltbg%3D (Pubitemid 46344656)
42. A.C. Zamora P.J. Wolters H.R. Collard, et al. 2008 Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease Respir Med 102 150 155 17822892 10.1016/j.rmed.2007.07.021 (Pubitemid 350151821)
43. A.J. Gerbino C.H. Goss J.A. Molitor 2008 Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease Chest 133 455 460 18071023 10.1378/chest.06-2861 1:CAS:528:DC%2BD1cXjtFemsLg%3D (Pubitemid 351272405)
44. J.J. Swigris A.L. Olson A. Fischer, et al. 2006 Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease Chest 130 30 36 16840379 10.1378/chest.130.1.30 1:CAS:528:DC%2BD28Xot1KjtL8%3D (Pubitemid 44116838)
45. F. Reichenberger J. Schauer K. Kellner, et al. 2001 Different expression of endothelin in the bronchoalveolar lavage in patients with pulmonary diseases Lung 179 163 174 11891606 10.1007/s004080000058 1:CAS:528:DC%2BD38XntFKltQ%3D%3D (Pubitemid 34033112)
46. T.E. King Jr J. Behr K.K. Brown, et al. 2008 BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis Am J Respir Crit Care Med 177 75 81 17901413 10.1164/rccm.200705-732OC 1:CAS:528:DC%2BD1cXht12mt7s%3D
47. J. Varga 2002 Scleroderma and Smads: dysfunctional Smad family dynamics culminating in fibrosis Arthritis Rheum 46 1703 1713 12124852 10.1002/art.10413 1:CAS:528:DC%2BD38XmtFWgs74%3D (Pubitemid 34774500)
48. C.P. Denton P.A. Merkel D.E. Furst, et al. 2006 Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192 Arthritis Rheum 56 323 333 10.1002/art.22289
49. J.H. Distler O. Distler 2009 Imatinib as a novel therapeutic approach for fibrotic disorders Rheumatology (Oxford) 48 2 4 10.1093/rheumatology/ken431 1:CAS:528:DC%2BD1cXhsVOgsL3N
50. C.E. Daniels M.C. Wilkes M. Edens, et al. 2004 Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis J Clin Invest 114 1308 1316 15520863 1:CAS:528:DC%2BD2cXpsFCgtrg%3D
51. A. Akhmetshina C. Dees M. Pileckyte, et al. 2008 Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis FASEB J 22 2214 2222 18326784 10.1096/fj.07-105627 1:CAS:528:DC%2BD1cXotlanurg%3D (Pubitemid 351948641)
52. A. Richter S.M. Puddicombe J.L. Lordan, et al. 2001 The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma Am J Respir Cell Mol Biol 25 385 391 11588018 1:CAS:528: DC%2BD3MXnvVemtbY%3D
53. A. Hancock L. Armstrong R. Gama A. Millar 1998 Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung Am J Respir Cell Mol Biol 18 60 65 9448046 1:CAS:528:DyaK1cXnslWjug%3D%3D (Pubitemid 128355347)
54. R.W. Simms J.H. Korn 2002 Cytokine directed therapy in scleroderma: rationale, current status, and the future Curr Opin Rheumatol 14 717 722 12410097 10.1097/00002281-200211000-00015 1:CAS:528:DC%2BD38XosFegurg%3D (Pubitemid 35191562)
55. Z. Zhu R.J. Homer Z. Wang, et al. 1999 Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production J Clin Invest 103 779 788 10079098 10.1172/JCI5909 1:CAS:528:DyaK1MXhvFaku70%3D
56. J.A. Belperio M. Dy M.D. Burdick, et al. 2002 Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis Am J Respir Cell Mol Biol 27 419 427 12356575 1:CAS:528:DC%2BD38XnvFGrsLc%3D
57. K. Dheda U.G. Lalloo B. Cassim G.M. Mody 2004 Experience with azathioprine in systemic sclerosis associated with interstitial lung disease Clin Rheumatol 23 306 309 15293090 1:STN:280:DC%2BD2czoslOjtA%3D%3D
58. O. Nadashkevich P. Davis M. Fritzler W. Kovalenko 2006 A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis Clin Rheumatol 25 205 212 16228107 10.1007/s10067-005-1157-y 1:STN:280:DC%2BD283ivFOjug%3D%3D (Pubitemid 43372319)
59. P.A. McSweeney R.A. Nash K.M. Sullivan, et al. 2002 High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes Blood 100 1602 1610 12176878 1:CAS:528:DC%2BD38Xmslyhtr4%3D
60. R.A. Nash P.A. McSweeney L.J. Crofford, et al. 2007 High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study Blood 110 1388 1396 17452515 10.1182/blood-2007-02-072389 1:CAS:528: DC%2BD2sXptFKlsLs%3D (Pubitemid 47281441)
61. van Laar J, Farge D, Tyndall A: ASTIS trial news: latest news. Available at http://www.astistrial.com/ASTISnews.HTM. Accessed December 15, 2008.
62. U.A. Walker A. Tyndall L. Czirjak, et al. 2007 Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database Ann Rheum Dis 66 754 763 17234652 10.1136/ard.2006.062901 1:STN:280:DC%2BD2s3pvFaksg%3D%3D (Pubitemid 46846694)