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 language||English (US)|
|Number of pages||10|
|Journal||Arthritis and rheumatism|
|State||Published - Jun 1999|
ASJC Scopus subject areas
- Immunology and Allergy
- Pharmacology (medical)