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

  1. Philip J. Clements1,*,
  2. Daniel E. Furst2,
  3. Weng-Kee Wong3,
  4. Maureen Mayes4,
  5. Barbara White5,
  6. Fredrick Wigley6,
  7. Michael H. Weisman7,
  8. Walter Barr8,
  9. Larry W. Moreland9,
  10. Thomas A. Medsger Jr.10,
  11. Virginia Steen11,
  12. Richard W. Martin12,
  13. David Collier13,
  14. Arthur Weinstein14,
  15. Edward Lally15,
  16. John Varga16,
  17. Steven Weiner1,
  18. Brian Andrews17,
  19. Micha Abeles18,
  20. James R. Seibold19

Article first published online: 26 APR 2001

DOI: 10.1002/1529-0131(199906)42:6<1194::AID-ANR16>3.0.CO;2-7

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 42, Issue 6, pages 1194–1203, June 1999

Additional Information

How to Cite

Clements, P. J., Furst, D. E., Wong, W.-K., Mayes, M., White, B., Wigley, F., Weisman, M. H., Barr, W., Moreland, L. W., Medsger Jr., T. A., Steen, V., Martin, R. W., Collier, D., Weinstein, A., Lally, E., Varga, J., Weiner, S., Andrews, B., Abeles, M. and Seibold, J. R. (1999), High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: Analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis & Rheumatism, 42: 1194–1203. doi: 10.1002/1529-0131(199906)42:6<1194::AID-ANR16>3.0.CO;2-7

Author Information

  1. 1

    University of California, Los Angeles, School of Medicine

  2. 2

    Virginia Mason Research Center, Seattle, Washington

  3. 3

    University of California, Los Angeles, School of Public Health

  4. 4

    Hutzel Hospital, Detroit, Michigan

  5. 5

    University of Maryland School of Medicine, Baltimore

  6. 6

    The Johns Hopkins University, Baltimore, Maryland

  7. 7

    University of California, San Diego, Medical Center

  8. 8

    Loyola University Stritch School of Medicine, Maywood, Illinois

  9. 9

    University of Alabama at Birmingham

  10. 10

    University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

  11. 11

    Georgetown University Medical Center, Washington, DC

  12. 12

    Michigan State University College of Human Medicine, Grand Rapids

  13. 13

    Denver Health Medical Center, and University of Colorado Health Sciences Center, Denver

  14. 14

    George Washington University Medical Center, Washington, DC

  15. 15

    Brown University School of Medicine, and Roger Williams General Hospital, Providence, Rhode Island

  16. 16

    University of Illinois, Chicago

  17. 17

    University of California, Irvine

  18. 18

    University of Connecticut Health Center, Farmington

  19. 19

    University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, New Jersey

*University of California, Los Angeles, School of Medicine, Department of Medicine/Rheumatology, 32-59 Rehabilitation Center, Box 951670, Los Angeles, CA 90095-1670

Publication History

  1. Issue published online: 26 APR 2001
  2. Article first published online: 26 APR 2001
  3. Manuscript Accepted: 15 JAN 1999
  4. Manuscript Received: 13 AUG 1998

Funded by

  • Scleroderma Foundation, Danvers, MA
  • United Scleroderma Foundation
  • Orphan Drug Program of the Food and Drug Administration
  • Arthritis Foundation
  • W. H. Conzen Endowment of the Schering-Plough Foundation
  • USPHS. Grant Numbers: M01-RR-00865, M01-RR-00827

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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 patients (10 developed SRC and 12 died). Of the 20 adverse event–related 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.

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