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

Open Access
Publisher Website
Google Scholar
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.