High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: Analysis of a two-year, double-blind, randomized, controlled clinical trial

Philip J. Clements*, Daniel E. Furst, Weng Kee Wong, Maureen Mayes, Barbara White, Fredrick Wigley, Michael H. Weisman, Walter Barr, Larry W. Moreland, Thomas A. Medsger, Virginia Steen, Richard W. Martin, David Collier, Arthur Weinstein, Edward Lally, John Varga, Steven Weiner, Brian Andrews, Micha Abeles, James R. Seibold

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

Abstract

Objective. To test the hypothesis that systemic sclerosis (SSc) patients taking high-dose D-penicillamine (D-Pen) would have greater softening of skin, lower frequency of renal crisis, and better survival than patients taking low-dose D-Pen. Methods. Seventeen centers enrolled 134 SSc patients with early (≤18 months) diffuse cutaneous scleroderma into a 2-year, double- blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus low-dose D-Pen (125 mg every other day). All 134 patients were followed up for a mean ±SD of 4.0 ± 1.1 years to assess the frequencies of new-onset scleroderma renal crisis (SRC) and mortality. Results. Sixty-eight patients completed 24 months of drug treatment. The course of the modified Rodnan skin thickness score in the 32 high-dose and the 36 low-dose D-Pen completers was not different at 24 months: the skin score dropped 4.8 ± 10.3 (mean ± SD) units in the high-dose group and 6.9 ± 8.4 units in the low-dose group (P = 0.384 by t-test; favoring low-dose D-Pen) from 20.4 ± 10.3 in the high-dose and 19.9 ± 6.6 in the low-dose D-Pen group at study entry. The incidences of SRC and mortality were not different (P > 0.38 by Cox proportional hazards and by chi-square test) in the 66 high-dose patients (8 developed SRC and 8 died) compared with the 68 low-dose patientss (10 developed SRC and 12 died). Of the 20 adverse eventrelated withdrawals, 80% occurred in the high-dose D- Pen group. Conclusion. The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Original languageEnglish (US)
Pages (from-to)1194-1203
Number of pages10
JournalArthritis and rheumatism
Volume42
Issue number6
DOIs
StatePublished - Jun 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: Analysis of a two-year, double-blind, randomized, controlled clinical trial'. Together they form a unique fingerprint.

Cite this