Innovative therapies for systemic sclerosis

Current Opinion in Rheumatology

Volumn 22, Issue 3, 2010, Pages 264-272

  Ong, Voon H ^a   Denton, Christopher P ^a  

^a ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Immune; Scleroderma; Systemic sclerosis; Treatments

Indexed keywords

ABATACEPT; ALEMTUZUMAB; ATORVASTATIN; BASILIXIMAB; BOSENTAN; CYCLOPHOSPHAMIDE; ENDOTHELIN RECEPTOR ANTAGONIST; HALOFUGINONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMATINIB; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PHOSPHODIESTERASE V INHIBITOR; PREDNISOLONE; PROSTACYCLIN DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; RAPAMYCIN; RITUXIMAB; ROSIGLITAZONE; SILDENAFIL; TOCILIZUMAB;

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; CARDIOTOXICITY; DIFFUSE SCLERODERMA; DRUG MECHANISM; EDEMA; EFFECTOR CELL; FATIGUE; HUMAN; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LIMITED SCLERODERMA; MYALGIA; NAUSEA; PATHOGENESIS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SYSTEMIC SCLEROSIS; TH17 CELL;

ANTIBODIES, MONOCLONAL; ANTIRHEUMATIC AGENTS; B-LYMPHOCYTES; DRUG DESIGN; ENZYME INHIBITORS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOLOGIC FACTORS; RHEUMATOLOGY; SCLERODERMA, SYSTEMIC; T-LYMPHOCYTES;

EID: 77950260569     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/BOR.0b013e328337c3d6     Document Type: Review

References (85)

1. Denton CP, Black CM. Targeted therapy comes of age in scleroderma. Trends Immunol 2005; 26:596-602.
2. Shand L, Lunt M, Nihtyanova S, et al. Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. Arthritis Rheum 2007; 56:2422-2431.
3. Nihtyanova SI, Tang EC, Coghlan JG, et al. Improved survival in systemic sclerosis is associated with better ascertainment of internal organ disease: a retrospective cohort study. QJM 2010; 103:109-115.
4. Quillinan NP, Denton CP. Disease-modifying treatment in systemic sclerosis: current status. Curr Opin Rheumatol 2009; 21:636-641.
5. Sondergaard K, Stengaard-Pedersen K, Zachariae H, et al. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin. Br J Rheumatol 1998; 37:304-310.
6. Sakkas LI, Xu B, Artlett CM, et al. Oligoclonal T cell expansion in the skin of patients with systemic sclerosis. J Immunol 2002; 168:3649-3659.
7. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med 2009; 361:888-898.
8. Rodriguez-ReynaTS, Furuzawa-Carballeda J, Cabiedes J, et al. Th17 polariza tion in systemic sclerosis is influenced by immunosuppressive treatment re gardless time of evolution [abstract]. Arthritis Rheum 2009; 60 (Suppl):420.
9. Radstake TR, van Bon L, Broen J, et al. The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes. PLoS One 2009; 4:e5903.
10. Sundrud MS, Koralov SB, Feuerer M, et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 2009; 324:1334-1338.
11. Pines M, Snyder D, Yarkoni S, et al. Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma. Biol Blood Marrow Transplant 2003; 9:417-425.
12. Kalogerou A, Gelou E, Mountantonakis S, et al. Early T cell activation in the skin from patients with systemic sclerosis. Ann Rheum Dis 2005; 64:1233-1235.
13. Schmidt K, Martinez-Gamboa L, Meier S, et al. Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients. Arthritis Res Ther 2009; 11:R111.
14. Degiannis D,Seibold JR, Czarnecki M, et al. Soluble interleukin-2 receptors in patients with systemic sclerosis: clinical and laboratory correlations. Arthritis Rheum 1990; 33:375-380.
15. Scherer HU, Burmester GR, Riemekasten G. Targeting activated T cells: successful use of anti-CD25 monoclonal antibody basiliximab in a patient with systemic sclerosis. Ann Rheum Dis 2006; 65:1245-1247.
16. Isaacs JD, Hazleman BL, Chakravarty K, et al. Monoclonal antibody therapy of diffuse cutaneous scleroderma with CAMPATH-1H. J Rheumatol 1996; 23:1103-1106.
17. + regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am J Transplant 2008; 8:793-802.
18. +T cells population studies. Roum Arch Microbiol Immunol 2009; 68:5-13.
19. Klein S, Kretz CC, Krammer PH, Kuhn A. CD127(low/\) and FoxP3(+) expression levels characterize different regulatory T-cell populations in human peripheral blood. J Invest Dermatol 2010; 130:492-499.
20. Radstake TR, van Bon L, Broen J, etal. Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFbeta expression. PLoS One 2009; 4:e5981.
21. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+CD25high regulatory cells in human peripheral blood. J Immunol 2001; 167:1245-1253.
22. Vonk MC, Marjanovic Z, van den Hoogen FH, et al. Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis. Ann Rheum Dis 2008; 67:98-104.
23. Fleming JN, Nash RA, McLeod DO, et al. Capillary regeneration in sclero-derma: stem cell therapy reverses phenotype? PLoS One 2008; 3:e1452.
24. Verrecchia F, Laboureau J, Verola O, et al. Skin involvement in scleroderma: where histological and clinical scores meet. Rheumatology (Oxford) 2007; 46:833-841.
25. Nash RA, McSweeney PA, Crofford LJ, etal. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007; 110:1388-1396.
26. Aschwanden M, Daikeler T, Jaeger KA, et al. Rapid improvement of nailfold capillaroscopy after intense immunosuppression for systemic sclerosis and mixed connective tissue disease. Ann Rheum Dis 2008; 67:1057-1059.
27. Smith V, Van Praet JT, Vandooren B, et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 2010; 69:193-197.
28. Lafyatis R, Kissin E, York M, et al. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 2009; 60:578-583.
29. Daoussis D, Liossis SN, Tsamandas AC, et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford) 2010; 49:271-280.
30. McGonagle D, Tan AL, Madden J, et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford) 2008; 47:552-553.
31. Brulhart L, Waldburger JM, Gabay C. Rituximab in the treatment of anti-synthetase syndrome. Ann Rheum Dis 2006; 65:974-975.
32. Sem M, Molberg O, Lund MB, Gran JT. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series. Rheumatology (Oxford) 2009; 48:968-971.
33. Yellin M, Paliienko I, Balanescu A, et al. A phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):414.
34. Nishimura M, Kuboi Y, Muramoto K, et al. Chemokines as novel therapeutic targets for inflammatory bowel disease. Ann N Y Acad Sci 2009; 1173:350-356.
35. Cipriani P, Franca Milia A, Liakouli V, et al. Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: pathogenetic implications. Arthritis Rheum 2006; 54:3022-3033.
36. Cipriani P, Guiducci S, Miniati I, et al. Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis. Arthritis Rheum 2007; 56:1994-2004.
37. Campioni D, Lo Monaco A, Lanza F, etal. CXCR4 pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis. Haematologica 2008; 93:1233-1237.
38. Keeley EC, Mehrad B, Strieter RM. Fibrocytes: bringing new insights into mechanisms of inflammation and fibrosis. Int J Biochem Cell Biol 2009 Oct 20. [Epub ahead of print]
39. Phillips RJ, Burdick MD, Hong K, et al. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 2004; 114:438-446.
40. Ortiz LA, Gambelli F, McBride C, etal. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 2003; 100:8407-8411.
41. Brooks WH, Le Dantec C, Pers JO, et al. Epigenetics and autoimmunity. J Autoimmun. 2010 Jan 4. [Epub ahead of print]
42. Wang Y, Fan PS, Kahaleh B. Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis Rheum 2006; 54:2271-2279.
43. Ghosh AK, Varga J. The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol 2007; 213:663-671.
44. Huber LC, Distler JH, Moritz F, etal. Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis. Arthritis Rheum 2007; 56:2755-2764.
45. Hemmatazad H, Rodrigues HM, Maurer B, et al. Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis. Arthritis Rheum 2009; 60:1519-1529.
46. Garber K. HDAC inhibitors overcome first hurdle. Nat Biotechnol 2007; 25:17-19.
47. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers. J Rheumatol 2008; 35:1801-1808.
48. Kuwana M, Okazaki Y, Kaburaki J. Long-term beneficial effects of statins on vascular manifestations in patients with systemic sclerosis registry [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):448.
49. Nguyen VA, Eisendle K, Gruber I, etal. Effect of the dual endothelin receptor antagonist bosentan on Raynaud's phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study. Rheumatology (Oxford). 2009 Dec 29. [Epub ahead of print]
50. Korn JH, Mayes M, Matucci Cerinic M, et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004; 50:3985-3993.
51. Garćia de la Peña-Lefebvre P, Rodŕiguez Rubio S, Valero Exposito M, et al. Long-term experience of bosentan for treating ulcers and healed ulcers in systemic sclerosis patients. Rheumatology (Oxford) 2008; 47:464-466.
52. Cardillo C, Schinzari F, Melina D, etal. Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis. Arthritis Rheum 2009; 60:1840-1844.
53. Fries R, Shariat K, von Wilmowsky H, Bohm M. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation 2005; 112:2980-2985.
54. Herrick AL, van den Hoogen F, Gabrielli A, et al. Modified-release sildenafil reduces Raynaud's attack frequency in systemic sclerosis [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):472.
55. Brueckner CS, Becker MO, Kroencke T, et al. Effect of sildenafil on digital ulcers in systemic sclerosis: analysis from a single center pilot study. Ann Rheum Dis 2009 Nov 8. [Epub ahead of print]
56. Baroni SS, Santillo M, Bevilacqua F, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 2006; 354:2667-2676.
57. Li M, Abdollahi A, Grone HJ, et al. Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model. Radiat Oncol 2009; 4:66.
58. Akhmetshina A, Venalis P, Dees C, et al. Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis. Arthritis Rheum 2009; 60:219-224.
59. Wang S, Wilkes MC, Leof EB, Hirschberg R. Noncanonical TGF-beta path-ways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol 2010; 298:F142-F149.
60. Yoshiji H, Noguchi R, Kuriyama S, etal. Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats. Am J Physiol Gastrointest Liver Physiol 2005; 288:G907-G913.
61. Olivieri A, Locatelli F, Zecca M, et al. Imatinib for refractory chronic graft-versus-host-disease with fibrotic features. Blood 2009; 114:709-718.
62. Magro L, Mohty M, Catteau B, et al. Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versus-host disease. Blood 2009; 114:719-722.
63. Gordon J, Mersten J, Lyman S, et al. Imatinib mesylate (gleevec) in the treatment of systemic sclerosis: interim results of a phase IIa, one year, open label clinical trial [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):414.
64. Gordon J, Vukelic S, Magro CM, et al. Histologic and molecular basis of improved skin scores in scleroderma patients treated with imatinib mesylate (Gleevec) [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):460.
65. Pope J, McBain D, Petrlich L, et al. A proof of concept trial of Gleevec (imatinib) in active diffuse scleroderma [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):608.
66. Kerkela? R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 2006; 12:908-916.
67. Shi-Wen X, Eastwood M, Stratton RJ, et al. Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts. Rheumatology (Oxford) 2010; 49:259-263.
68. Kapoor M, McCann M, Liu S, etal. Loss of PPARg in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum 2009; 60:2822-2829.
69. Wu M, Melichian DS, Chang E, et al. Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator activated receptor-gamma. Am J Pathol 2009; 174:519-533.
70. Harris TE, Lawrence JC Jr. TOR signaling. Sci STKE 2003; 2003:re15.
71. Shegogue D, Trojanowska M. Mammalian target of rapamycin positively regulates collagen type I production via a phosphatidylinositol 3-kinase-independent pathway. J Biol Chem 2004; 279:231 66-23175.
72. Mehrad B, Burdick MD, Strieter RM. Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int J Biochem Cell Biol 2009; 41:1708-1718.
73. Fried L, Kirsner RS, Bhandarkar S, Arbiser JL Efficacy of rapamycin in scleroderma: a case study. Lymphat Res Biol 2008; 6 (3-4):217-219.
74. Buschhausen L, Kamm M, Arns W, et al. Successful treatment of a severe case of idiopathic pulmonary fibrosis with rapamycin. Med Klin (Munich) 2005; 100:161-164.
75. Su TI, Khanna D, Furst DE, et al. Rapamycin versus methotrexate in early diffuse systemic sclerosis: results from a randomized, single-blind pilot study. Arthritis Rheum 2009; 60:3821-3830.
76. Denton CP, Merkel PA, Furst DE, et al. Recombinant human antitransforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-1 92. Arthritis Rheum 2007; 56:323-333.
77. Nihtyanova SI, Brough GM, Black CM, Denton CP. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis: a retrospective analysis. Rheumatology (Oxford) 2007; 46:442-445.
78. Derk CT, Grace E, Shenin M, et al. A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis. Rheu matology (Oxford) 2009; 48:1595-1599.
79. Zamora AC, Wolters PJ, Collard HR, et al. Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease. Respir Med 2008; 102:150-155.
80. Liossis SN, Bounas A, Andonopoulos AP. Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology (Oxford) 2006; 45:1005-1008.
81. Cuomo G, Abignano G, Iudici G, et al. Effectiveness and safety of mycophenolate mofetil in the treatment of interstitial lung disease in patients with systemic sclerosis [abstract]. Arthritis Rheum 2009; 60 (Suppl 10):468.
82. NakaT, Nishimoto N. KishimotoT: the paradigm of IL-6: from basic science to medicine. Arthritis Res 2002; 4 (Suppl 3):S233-S242.
83. Kawaguchi Y, Hara M, Wright TM. Endogenous IL-1 from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. J Clin Invest 1999; 103:1253-1260.
84. Luckett LR, Gallucci RM. Interleukin-6 (IL-6) modulates migration and matrix metalloproteinase function in dermal fibroblasts from IL-6KO mice. Br J Dermatol 2007; 156:1163-1171.
85. Ong V, Nihtyanova S, Black CM, et al. A clinically defined subset of dcSSc is associated with elevated serum IL-6 level [abstract]. Arthritis Rheum 2009; 60 (Suppl):440.