Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Journal of Clinical Investigation

Volumn 125, Issue 7, 2015, Pages 2795-2807

  Rice, Lisa M ^a   Padilla, Cristina M ^a   McLaughlin, Sarah R ^a   Mathes, Allison ^a   Ziemek, Jessica ^a   Goummih, Salma ^a   Nakerakanti, Sashidhar ^a   York, Michael ^a   Farina, Giuseppina ^a   Whitfield, Michael L ^b   Spiera, Robert F ^c   Christmann, Romy B ^a   Gordon, Jessica K ^c   Weinberg, Janice ^d   Simms, Robert W ^a   Lafyatis, Robert ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HOSPITAL FOR SPECIAL SURGERY   (United States)

^c DARTMOUTH MEDICAL SCHOOL   (United States)

^d BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAM METALLOPEPTIDASE DOMAIN 12; BIOLOGICAL MARKER; CADHERIN; CADHERIN 11; CARTILAGE OLIGOMERIC MATRIX PROTEIN; COLLAGEN; COLLAGEN TYPE 10; COLLAGEN TYPE 10 ALPHA 1; COLLAGEN XI ALPHA 1; CONNECTIVE TISSUE GROWTH FACTOR; FIBRONECTIN; FRESOLIMUMAB; HEMOGLOBIN; METALLOPROTEINASE; NILOTINIB; PLASMINOGEN ACTIVATOR; PLASMINOGEN ACTIVATOR PROTEIN 1; PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; SERPINE1 PROTEIN; THROMBOSPONDIN 1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; COMP PROTEIN, HUMAN; GENETIC MARKER; MONOCLONAL ANTIBODY;

ABNORMAL PAP SMEAR; ADULT; ANEMIA; ANEMIA OF CHRONIC DISEASE; ARTHRALGIA; ARTICLE; BLEEDING; BLOODSHOT EYE; CAUSE OF DEATH; CHRONIC DISEASE; CLINICAL ARTICLE; CONGESTIVE HEART FAILURE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE DURATION; DRUG INDUCED HEADACHE; DRUG SAFETY; DYSPNEA; EPISTAXIS; EYE DISEASE; FACE DISORDER; FACE SWELLING; FEMALE; FOLLOW UP; FORCED VITAL CAPACITY; GASTROINTESTINAL HEMORRHAGE; GENE EXPRESSION; GINGIVA BLEEDING; GYNECOLOGIC DISEASE; HEART FAILURE; HEART MUSCLE BIOPSY; HEART MUSCLE FIBROSIS; HEME POSITIVE STOOL; HEMOGLOBIN BLOOD LEVEL; HOSPITALIZATION; HUMAN; HUMAN TISSUE; INJECTION SITE REACTION; INTERSTITIAL LUNG DISEASE; INTRAOCULAR HEMORRHAGE; MALE; MIDDLE AGED; MYOFIBROBLAST; OPEN STUDY; PAPANICOLAOU TEST; PRIORITY JOURNAL; RETICULOCYTOSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SKIN BIOPSY; SKIN DISEASE; STOMACH ANTRUM VASCULAR ECTASIA; SUBCONJUNCTIVAL HEMORRHAGE; SYSTEMIC SCLEROSIS; TENDINITIS; VOMITING; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; GENETIC MARKER; GENETICS; PATHOLOGY; SCLERODERMA, SYSTEMIC; TREATMENT OUTCOME;

ADULT; ANTIBODIES, MONOCLONAL; CARTILAGE OLIGOMERIC MATRIX PROTEIN; FEMALE; GENE EXPRESSION; GENETIC MARKERS; HUMANS; MALE; MIDDLE AGED; MYOFIBROBLASTS; SCLERODERMA, SYSTEMIC; THROMBOSPONDIN 1; TRANSFORMING GROWTH FACTOR BETA; TREATMENT OUTCOME;

EID: 84936791793     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI77958     Document Type: Article

References (51)

1. Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB. Type β transforming growth factor: A bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985;82(1):119-123.
2. Roberts AB, et al. Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986;83(12):4167-4171.
3. Roberts AB, Heine UI, Flanders KC, Sporn MB. Transforming growth factor-β. Major role in regulation of extracellular matrix. Ann N Y Acad Sci. 1990;580:225-232.
4. Penttinen RP, Kobayashi S, Bornstein P. Transforming growth factor β increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988;85(4):1105-1108.
5. Derynck R, Miyaono K, eds. The TGF-Beta Family. Cold Spring Harbor Monograph Series 50. Cold Spring Harbor, New York, USA: Cold Spring Harbor Laboratory Press; 2007.
6. Varga J, Denton CP, Wigley FM, eds. Scleroderma: From Pathogenesis to Comprehensive Management. New York, New York, USA: Springer; 2012.
7. Tashkin DP, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655-2666.
8. van Laar JM, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: A randomized clinical trial. JAMA. 2014;311(24):2490-2498.
9. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199-210.
10. Clements PJ, et al. Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial. Arthritis Rheum. 2000;43(11):2445-2454.
11. Varga J, Abraham D. Systemic sclerosis: A prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117(3):557-567.
12. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.
13. Merkel PA, et al. Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2012;64(10):3420-3429.
14. Matucci-Cerinic M, Steen VD, Furst DE, Seibold JR. Clinical trials in systemic sclerosis: lessons learned and outcomes. Arthritis Res Ther. 2007;9(suppl 2):S7.
15. Farina G, Lafyatis D, Lemaire R, Lafyatis R. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2010;62(2):580-588.
16. Sobanski V, et al. Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: new data from a French cohort and a systematic review and meta-analysis. Arthritis Rheumatol. 2014;66(2):407-417.
17. Okano Y, Steen VD, Medsger TA Jr. Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med. 1993;119(10):1005-1013.
18. Amjadi S, et al. Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum. 2009;60(8):2490-2498.
19. Igarashi A, et al. Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis. J Invest Dermatol. 1995;105(2):280-284.
20. Wu M, et al. Identification of cadherin-11 as a mediator of dermal fibrosis and possible role in systemic sclerosis. Arthritis Rheumatol. 2013;66(4):1010-1021.
21. Hecker L, et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat Med. 2009;15(9):1077-1081.
22. Mehlhorn AT, et al. Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells. Cell Prolif. 2007;40(6):809-823.
23. Zhou XD, Xiong MM, Tan FK, Guo XJ, Arnett FC. SPARC, an upstream regulator of connective tissue growth factor in response to transforming growth factor beta stimulation. Arthritis Rheum. 2006;54(12):3885-3889.
24. Rice LM, et al. A longitudinal biomarker for the extent of skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. In press.
25. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-β 1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122(1):103-111.
26. Kissin EY, Merkel PA, Lafyatis R. Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis. Arthritis Rheum. 2006;54(11):3655-3660.
27. Lund LR, et al. Transforming growth factor-β is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. EMBO J. 1987;6(5):1281-1286.
28. Meune C, Vignaux O, Kahan A, Allanore Y. Heart involvement in systemic sclerosis: evolving concept and diagnostic methodologies. Arch Cardiovasc Dis. 2010;103(1):46-52.
29. Gewin L, Zent R. How does TGF-beta mediate tubulointerstitial fibrosis? Semin Nephrol. 2012;32(3):228-235.
30. Inagaki Y, Higashiyama R, Higashi K. Novel antifibrotic modalities for liver fibrosis: molecular targeting and regenerative medicine in fibrosis therapy. J Gastroenterol Hepatol. 2012; 27(suppl 2):85-88.
31. Maher TM. Idiopathic pulmonary fibrosis: pathobiology of novel approaches to treatment. Clin Chest Med. 2012;33(1):69-83.
32. Sonnylal S, et al. Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis. Arthritis Rheum. 2010;62(5):1523-1532.
33. Wahl SM, et al. Transforming growth factor type β induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987;84(16):5788-5792.
34. Gerber EE, et al. Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature. 2013;503(7474):126-130.
35. Kim YM, et al. Proteomic identification of ADAM12 as a regulator for TGF-β1-induced differentiation of human mesenchymal stem cells to smooth muscle cells. PLoS One. 2012;7(7):e40820.
36. Negoescu A, Lafeuillade B, Pellerin S, Chambaz EM, Feige JJ. Transforming growth factors β stimulate both thrombospondin-1 and CISP/thrombospondin-2 synthesis by bovine adrenocortical cells. Exp Cell Res. 1995;217(2):404-409.
37. Atfi A, et al. The disintegrin and metalloproteinase ADAM12 contributes to TGF-β signaling through interaction with the type II receptor. J Cell Biol. 2007;178(2):201-208.
38. Dulauroy S, Di Carlo SE, Langa F, Eberl G, Peduto L. Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med. 2012;18(8):1262-1270.
39. Denton CP, et al. 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. 2007;56(1):323-333.
40. Rapoza ML, Fu D, Sendak RA. Development of an in vitro potency assay for therapeutic TGFβ antagonists: The A549 cell bioassay. J Immunol Methods. 2006;316(1):18-26.
41. Qu X, et al. Regulation of renal fibrosis by Smad3 thr388 phosphorylation. Am J Pathol. 2014;184(4):944-952.
42. Lee HS. Mechanisms and consequences of TGF-ss overexpression by podocytes in progressive podocyte disease. Cell Tissue Res. 2012;347(1):129-140.
43. Kim JH, Kim BK, Moon KC, Hong HK, Lee HS. Activation of the TGF-β/Smad signaling pathway in focal segmental glomerulosclerosis. Kidney Int. 2003;64(5):1715-1721.
44. Bennett MR, Czech KA, Arend LJ, Witte DP, Devarajan P, Potter SS. Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli. Nephron Exp Nephrol. 2007;107(1):e30-e40.
45. Stevenson JP, et al. Immunological effects of the TGFbeta-blocking antibody GC1008 in malignant pleural mesothelioma patients. Oncoimmunology. 2013;2(8):e26218.
46. Morris JC, et al. Phase I study of GC1008 (fresolimumab): A human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS One. 2014;9(3):e90353.
47. Trachtman H, et al. A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int. 2011;79(11):1236-1243.
48. Elhai M, Meune C, Avouac J, Kahan A, Allanore Y. Trends in mortality in patients with systemic sclerosis over 40 years: A systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2012;51(6):1017-1026.
49. [No authors listed]. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581-590.
50. LeRoy EC, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988;15(2):202-205.
51. de Hoon MJ, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics. 2004;20(9):1453-1454.