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

Objective, To test the hypothesis that systemic sclerosis (SSc) patients ta king 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 (less than or equal to 18 months) diffuse cutaneous scleroderma into a 2-year, double- blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus l ow-dose D-Pen (125 mg every other day), All 134 patients were followed up f or a mean +/- SD of 4.0 +/- 1.1 years to assess the frequencies of new-onse t scleroderma renal crisis (SRC) and mortality, Results. Sixty-eight patients completed 24 months of drug treatment. The co urse of the modified Rodnan skin thickness score in the 32 high-dose and th e 36 low-dose D-Pen completers was not different at 24 months: the skin sco re 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-dos e 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 mor tality in the high-dose D-Pen group were not different from those in the lo w-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high dose D-Pen patients. Although this study cannot answe r 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.