Interferon-alpha 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 Feb;42(2):299-305. doi: 10.1002/1529-0131(199902)42:2<299::AID-ANR12>3.0.CO;2-R.

Abstract

Objective: To determine whether interferon-alpha (IFNalpha) reduces the severity of skin involvement in early (<3 years) diffuse scleroderma.

Methods: In a randomized, placebo-controlled, double-blind trial, 35 patients with early scleroderma received subcutaneous injections of either IFNalpha (13.5 x 10(6) units per week in divided doses) or indistinguishable placebo. Outcomes assessed were the modified Rodnan skin score, as determined by a single observer at baseline, 6 months, and 12 months, as well as data on renal, cardiac, and lung function. Pre- and posttreatment skin biopsy samples were analyzed and blood was obtained for assessment of procollagen peptide levels.

Results: There were 11 withdrawals from the IFNalpha group and 3 from the placebo group due to either toxicity, lack of efficacy, or death. In the intent-to-treat analysis, there was a greater improvement in the skin score in the placebo group between 0 and 12 months (mean change IFNalpha -4.7 versus placebo -7.5; P = 0.36). There was also a greater deterioration in lung function in patients receiving active therapy, as assessed by either the forced vital capacity (mean change IFNalpha -8.2 versus placebo +1.3; P = 0.01) or the diffusing capacity for carbon monoxide (mean change IFNalpha -9.3 versus placebo +4.7; P = 0.002). Skin biopsy showed no significant decrease in collagen synthesis in the IFNalpha group, and no significant differences in the levels of procollagen peptides were seen between the 2 groups.

Conclusion: This study suggests that IFNalpha is of no value in the treatment of scleroderma, and that it may in fact be deleterious.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Collagen / blood
  • Collagen / metabolism
  • Collagen Type I
  • Dermis / cytology
  • Dermis / metabolism
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Injections, Subcutaneous
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptides / blood
  • Procollagen / blood
  • Recombinant Proteins
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / pathology
  • Skin / drug effects
  • Skin / pathology
  • Treatment Outcome

Substances

  • Collagen Type I
  • Interferon alpha-2
  • Interferon-alpha
  • Peptide Fragments
  • Peptides
  • Procollagen
  • Recombinant Proteins
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Collagen