A multicenter, randomized, double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease.

OBJECTIVE To investigate the safety and efficacy of oral bovine type I collagen (CI) treatment in patients who have had diffuse cutaneous systemic sclerosis (dcSSc; scleroderma) for <or=10 years. METHODS One hundred sixty-eight patients with dcSSc were enrolled in a double-blind, placebo-controlled trial of oral CI (500 microg/day) or placebo administered over 12 months, with a followup visit at month 15. The primary outcome was the modified Rodnan skin thickness score (MRSS). Other clinical and immune system parameters were also assessed. RESULTS Intent-to-treat and modified intent-to-treat analyses showed that for the total population of patients with dcSSc, there were no significant differences in the mean change in MRSS or other key clinical parameters between the CI and placebo treatment groups at 12 months or at 15 months. However, in a subanalysis of the available data at month 15, the CI-treated group of patients with late-phase dcSSc experienced a significant reduction in the MRSS compared with that in the placebo-treated patients with late-phase dcSSc (change in MRSS at month 15 -7.9 versus -2.9; P = 0.0063). CONCLUSION Although the results from this trial did not meet the primary outcome goals, the findings from exploratory analyses indicated that CI treatment may benefit patients with late-phase dcSSc. This new treatment strategy and preliminary clinical observations in patients with dcSSc need to be corroborated.

[1]  Mark Lunt,et al.  Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. , 2007, Arthritis and rheumatism.

[2]  B. White,et al.  Cytokine regulation of pulmonary fibrosis in scleroderma. , 2003, Cytokine & growth factor reviews.

[3]  S. Jimenez,et al.  Oligoclonal T Cell Expansion in the Skin of Patients with Systemic Sclerosis1 , 2002, The Journal of Immunology.

[4]  T. Medsger,et al.  Improvement in skin thickening in systemic sclerosis associated with improved survival. , 2001, Arthritis and rheumatism.

[5]  J. Thompson,et al.  Juvenile arthritis and autoimmunity to type II collagen. , 2001, Arthritis and rheumatism.

[6]  Richard W. Martin,et al.  Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial. , 2000, Arthritis and rheumatism.

[7]  L. Carbone,et al.  Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen. , 2000, Arthritis and rheumatism.

[8]  P. Tugwell,et al.  Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group. , 1999, Arthritis and rheumatism.

[9]  S. Atamas,et al.  Interleukin 4 in Systemic Sclerosis: Not Just an Increase , 1999, Clinical Diagnostic Laboratory Immunology.

[10]  R. Wise,et al.  Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. , 1999, Arthritis and rheumatism.

[11]  Richard W. Martin,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. , 1999, Arthritis and rheumatism.

[12]  L. Carbone,et al.  Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid arthritis. , 1999, Arthritis and rheumatism.

[13]  R. Scorza,et al.  Increased interferon‐gamma (IFN‐γ) levels produced in vitro by alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon , 1999, Clinical and experimental immunology.

[14]  B. White,et al.  Immunopathogenesis of systemic sclerosis. , 1996, Rheumatic diseases clinics of North America.

[15]  D. Trentham,et al.  A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. , 1996, Arthritis and rheumatism.

[16]  H. Weiner,et al.  Intraocular Inflammatory Disease (Uveitis) and the Use of Oral Tolerance. , 1996, Annals of the New York Academy of Sciences.

[17]  Richard W. Martin,et al.  Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. , 1995, The Journal of rheumatology.

[18]  P. Jeffery,et al.  Fibrosing alveolitis in systemic sclerosis: increase in memory T-cells in lung interstitium. , 1995, The European respiratory journal.

[19]  S. Pahwa,et al.  Augmented interleukin-6 secretion in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis. , 1994, Annals of allergy.

[20]  K. Takeda,et al.  Decreased collagenase expression in cultured systemic sclerosis fibroblasts. , 1994, The Journal of investigative dermatology.

[21]  A. Silman,et al.  Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. , 1993, The Journal of rheumatology.

[22]  H. Weiner,et al.  Effects of oral administration of type II collagen on rheumatoid arthritis. , 1993, Science.

[23]  H. Weiner,et al.  Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. , 1993, Science.

[24]  A. Miller,et al.  Lung function testing: selection of reference values and interpretative strategies. , 1992, The American review of respiratory disease.

[25]  A. Freemont,et al.  Sequential dermal microvascular and perivascular changes in the development of scleroderma , 1992, The Journal of pathology.

[26]  C. Mele,et al.  Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis. , 1991, Arthritis and rheumatism.

[27]  H. Claman.  Mast cell changes in a case of rapidly progressive scleroderma-ultrastructural analysis. , 1989, The Journal of investigative dermatology.

[28]  J F Fries,et al.  The clinical value of the Stanford Health Assessment Questionnaire Functional Disability Index in patients with rheumatoid arthritis. , 1988, The Journal of rheumatology.

[29]  D. Johns,et al.  Single breath carbon monoxide diffusing capacity (transfer factor) , 1988, The American review of respiratory disease.

[30]  E. Leroy,et al.  Cellular immunity to collagen and laminin in scleroderma. , 1985, Arthritis and rheumatism.

[31]  T. Whiteside,et al.  Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. , 1984, Arthritis and rheumatism.

[32]  A. Masi.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). , 1980, Bulletin on the rheumatic diseases.

[33]  James F. Fries,et al.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. , 1980, Arthritis and rheumatism.

[34]  J. R. Reeves,et al.  Cellular infiltrates in scleroderma skin. , 1977, Arthritis and rheumatism.

[35]  A. Kang,et al.  Evidence for cell-mediated immunity to collagen in progressive systemic sclerosis. , 1976, The Journal of laboratory and clinical medicine.

[36]  J. Ware,et al.  Interpreting SF&-36 summary health measures: A response , 2004, Quality of Life Research.

[37]  N. Mitchison,et al.  Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial. , 1996, Arthritis and rheumatism.

[38]  J. Hankinson,et al.  American Thoracic Society. Single-breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique--1995 update. , 1995, American journal of respiratory and critical care medicine.