Recombinant human anti-transforming growth factor β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

Arthritis and Rheumatism

Volumn 56, Issue 1, 2007, Pages 323-333

  Denton, Christopher P ^a,p   Merkel, Peter A ^b   Furst, Daniel E ^c,d   Khanna, Dinesh ^c,d   Emery, Paul ^e   Hsu, Vivien M ^f   Silliman, Nancy ^g   Streisand, James ^g   Powell, John ^h   Åkesson, Anita ⁱ   Coppock, John ^j   Van Den Hoogen, Frank ^k   Herrick, Ariane ^l   Mayes, Maureen D ^m   Veale, Douglas ⁿ   Haas, Joanna ^g   Ledbetter, Stephen ^g   Korn, Joseph H ^q   Black, Carol M ^a   Seibold, James R ^o  

^a ROYAL FREE HOSPITAL   (United Kingdom)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CINCINNATI   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF LEEDS   (United Kingdom)

^f UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY   (United States)

^g Genzyme   (United States)

^h MEDIMMUNE LTD   (United Kingdom)

ⁱ LUND UNIVERSITY HOSPITAL   (Sweden)

^j WALSGRAVE HOSPITAL   (United Kingdom)

^k RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^l HOPE HOSPITAL   (United Kingdom)

^m UNIVERSITY OF TEXAS   (United States)

ⁿ ST VINCENT S UNIVERSITY HOSPITAL   (Ireland)

^o UNIVERSITY OF MICHIGAN   (United States)

^p ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^q NONE

more..

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; COLLAGEN TYPE 1; COLLAGEN TYPE 3; CYCLOPHOSPHAMIDE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; INTERLEUKIN 2 RECEPTOR; MESSENGER RNA; METELIMUMAB; PLACEBO; PROCOLLAGEN; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; VASODILATOR AGENT;

ADULT; AGED; ANEMIA; ARTICLE; BONE PAIN; CARDIOVASCULAR DISEASE; CLINICAL ARTICLE; CLINICAL TRIAL; COHORT ANALYSIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CUTANEOUS PARAMETERS; DEATH; DISEASE COURSE; DISEASE DURATION; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FEMALE; GASTROINTESTINAL DISEASE; GASTROINTESTINAL HEMORRHAGE; HUMAN; IMMUNOTHERAPY; INFECTION; INJECTION SITE REACTION; KIDNEY DISEASE; LUNG DISEASE; MALE; MODIFIED RODNAN SKIN THICKNESS SCORE; MORBIDITY; MULTICENTER STUDY; MYALGIA; PATIENT MOBILITY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; REPEATED DRUG DOSE; SCLERODERMA HEALTH ASSESSMENT QUESTIONNAIRE; SCORING SYSTEM; SIDE EFFECT; SKIN; SKIN BIOPSY; SKIN ULCER; SYSTEMIC SCLEROSIS; TREATMENT OUTCOME; WEIGHT REDUCTION;

ADULT; ANTIBODIES, MONOCLONAL; BIOLOGICAL MARKERS; COLLAGEN TYPE I; COLLAGEN TYPE III; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEALTH STATUS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFUSIONS, INTRAVENOUS; INTERNATIONAL COOPERATION; MALE; MIDDLE AGED; QUESTIONNAIRES; RECOMBINANT PROTEINS; RNA, MESSENGER; SCLERODERMA, DIFFUSE; SKIN; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TREATMENT OUTCOME;

EID: 33846250366     PISSN: 00043591     EISSN: None     Source Type: Journal    
DOI: 10.1002/art.22289     Document Type: Article

References (38)

1. Higley H, Persichitte K, Chu S, Waegell W, Vancheeswaran R, Black C. Immunocytochemical localization and serologic detection of transforming growth factor β1: association with type I procollagen and inflammatory cell markers in diffuse and limited systemic sclerosis, morphea, and Raynaud's phenomenon. Arthritis Rheum 1994;37:278-88.
2. Querfeld C, Eckes B, Huerkamp C, Krieg T, Sollberg S. Expression of TGF-β1, -β2 and -β3 in localized and systemic scleroderma. J Dermatol Sci 1999;21:13-22.
3. Yamane K, Ihn H, Kubo M, Tamaki K. Increased transcriptional activities of transforming growth factor β receptors in scleroderma fibroblasts. Arthritis Rheum 2002;46:2421-8.
4. Shi-wen X, Pennington D, Holmes A, Leask A, Bradham D, Beauchamp JR, et al. Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis. Exp Cell Res 2000;259:213-24.
5. Ruzek MC, Jha S, Ledbetter S, Richards SM, Garman RD. A modified model of graft-versus-host-induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease. Arthritis Rheum 2004;50:1319-31.
6. Denton CP, Black CM. Scleroderma-clinical and pathological advances [review]. Best Pract Res Clin Rheumatol 2004;18:271-90.
7. Furst DE, Clements PJ, Hillis S, Lachenbruch PA, Miller BL, Sterz MG, et al. Immunosuppression with chlorambucil, versus placebo, for scleroderma: results of a three-year, parallel, randomized, double-blind study. Arthritis Rheum 1989;32:584-93.
8. Pope JE, Bellamy N, Seibold JR, Baron M, Ellman M, Carette S, et al. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 2001;44:1351-8.
9. Van den Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, van Lier HJ, van de Putte LB. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 1996;35:364-72.
10. Black CM, Silman AJ, Herrick AI, Denton CP, Wilson H, Newman J, et al. Interferon-α does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1999;42:299-305.
11. Clements PJ, Furst DE, Wong WK, Mayes M, White B, Wigley F, et al. 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 1999;42:1194-203.
12. Polisson RP, Gilkeson GS, Pyun EH, Pisetsky DS, Smith EA, Simon LS. A multicenter trial of recombinant human interferon γ in patients with systemic sclerosis: effects on cutaneous fibrosis and interleukin 2 receptor levels. J Rheumatol 1996;23:654-8.
13. Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, et al. Recombinant human relaxin in the treatment of scleroderma: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000;132:871-9.
14. Kyriakidi M, Ioannidis JP. Design and quality considerations for randomized controlled trials in systemic sclerosis. Arthritis Rheum 2002;47:73-81.
15. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581-90.
16. White B, Bauer EA, Goldsmith LA, Hochberg MC, Katz LM, Korn JH, et al. Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. Arthritis Rheum 1995;38:351-60.
17. Seibold JR. Clinical trials: types, design, and end-points. Curr Opin Rheumatol 2001;13:512-5.
18. Clements P, Lachenbruch P, Seibold J, White B, Weiner S, Martin R, et al. Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 1995;22:1281-5.
19. Steen VD, Medsger TA Jr. The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis. Arthritis Rheum 1997;40:1146-51.
20. Steen VD, Medsger TA Jr. The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 1997;40:1984-91.
21. Massague J, Chen YG. Controlling TGFβ signalling. Genes Dev 2000;14:627-44.
22. Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, et al, for the Scleroderma Clinical Trials Consortium. Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis Rheum 2002;46:2410-20.
23. Denton CP, Abraham DJ. Transforming growth factor-β and connective tissue growth factor: key cytokines in scleroderma pathogenesis. Curr Opin Rheumatol 2001;13:505-11.
24. Santiago B, Gutierrez-Canas I, Dotor J, Palao G, Lasarte JJ, Ruiz J, et al. Topical application of a peptide inhibitor of transforming growth factor-β1 ameliorates bleomycin-induced skin fibrosis. J Invest Dermatol 2005;125:450-5.
25. Denton CP, Lindahl GE, Khan K, Shiwen X, Ong VH, Gaspar NJ, et al. Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type II transforming growth factor-β receptor (TβRIIΔK). J Biol Chem 2005;280:16053-65.
26. McCormick LL, Zhang Y, Tootell E, Gilliam AC. Anti-TGF-β treatment prevents skin and lung fibrosis in murine sclerodermatous graft-versus-host disease: a model for human scleroderma. J Immunol 1999;163:5693-9.
27. Zhang Y, McCormick LL, Gilliam AC. Latency-associated peptide prevents skin fibrosis in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol 2003;121:713-9.
28. Li JH, Zhu HJ, Huang XR, Lai KN, Johnson RJ, Lan HY. Smad7 inhibits fibrotic effect of TGF-β on renal tubular epithelial cells by blocking Smad2 activation. J Am Soc Nephrol 2002;13:1464-72.
29. Elliott RL, Blobe GC. Role of transforming growth factor β in human cancer. J Clin Oncol 2005;23:2078-93.
30. Tang B, Vu M, Booker T, Santner SJ, Miller FR, Anver MR, et al. TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest 2003;112:1116-24.
31. Merkel PA, Clements PJ, Reveille JD, Suarez-Almazor ME, Valentini G, Furst DE. Current status of outcome measure development for clinical trials in systemic sclerosis: report from OMERACT 6. J Rheumatol 2003;30:1630-47.
32. Steen VD, Medsger TA Jr. Improvement in skin thickening in systemic sclerosis associated with improved survival. Arthritis Rheum 2001;44:2828-35.
33. Cole JC, Motivala SJ, Khanna D, Lee JY, Paulus HE, Irwin MR. Validation of single-factor structure and scoring protocol for the Health Assessment Questionnaire-Disability Index. Arthritis Rheum 2005;53:536-42.
34. Claman HN, Giorno RC, Seibold JR. Endothelial and fibroblastic activation in scleroderma: the myth of the "uninvolved skin." Arthritis Rheum 1991;34:1495-501.
35. Balbir-Gurman A, Denton CP, Nichols B, Knight CJ, Nahir AM, Martin G, et al. Non-invasive measurement of biomechanical skin properties in systemic sclerosis. Ann Rheum Dis 2002;61:237-41.
36. Whitfield ML, Finlay DR, Murray JI, Troyanskaya OG, Chi JT, Pergamenschikov A, et al. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A 2003;100:12319-24.
37. Dziadzio M, Smith RE, Abraham DJ, Stratton RJ, Gabrielli A, Black CM, et al. Serological assessment of type I collagen burden in scleroderma spectrum disorders: a systematic review. Clin Exp Rheumatol 2004;22:356-67.
38. Steen VD, Engel EE, Charley MR, Medsger TA Jr. Soluble serum interleukin 2 receptors in patients with systemic sclerosis. J Rheumatol 1996;23:646-9.