High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial.
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 (< or =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.


CONCLUSIONS
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.
Clements
P J
PJ
Department of Medicine/Rheumatology, University of California, Los Angeles, School of Medicine, 90095-1670, USA.
Furst
D E
DE
Wong
W K
WK
Mayes
M
M
White
B
B
Wigley
F
F
Weisman
M H
MH
Barr
W
W
Moreland
L W
LW
Medsger
T A
TA
Steen
V
V
Martin
R W
RW
Collier
D
D
Weinstein
A
A
Lally
E
E
Varga
J
J
Weiner
S
S
Andrews
B
B
Abeles
M
M
Seibold
J R
JR
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000008:administration & dosage* / Q000009:adverse effects; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D011795:Surveys and Questionnaires; D015996:Survival Rate; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D003402:Creatine Kinase; D010396:Penicillamine