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. 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.
RCT Entities:
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. 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-Penpatients. 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.
Authors: M Binks; J R Passweg; D Furst; P McSweeney; K Sullivan; C Besenthal; J Finke; H H Peter; J van Laar; F C Breedveld; W E Fibbe; D Farge; E Gluckman; F Locatelli; A Martini; F van den Hoogen; L van de Putte; A V Schattenberg; R Arnold; P A Bacon; P Emery; I Espigado; B Hertenstein; F Hiepe; A Kashyap; I Kötter; A Marmont; A Martinez; M J Pascual; A Gratwohl; H G Prentice; C Black; A Tyndall Journal: Ann Rheum Dis Date: 2001-06 Impact factor: 19.103
Authors: Peter A McSweeney; Richard A Nash; Keith M Sullivan; Jan Storek; Leslie J Crofford; Roger Dansey; Maureen D Mayes; Kevin T McDonagh; J Lee Nelson; Theodore A Gooley; Leona A Holmberg; C S Chen; Mark H Wener; Katherine Ryan; Julie Sunderhaus; Ken Russell; John Rambharose; Rainer Storb; Daniel E Furst Journal: Blood Date: 2002-09-01 Impact factor: 22.113
Authors: P A Merkel; N P Silliman; P J Clements; C P Denton; D E Furst; M D Mayes; J E Pope; R P Polisson; J B Streisand; J R Seibold Journal: Arthritis Rheum Date: 2012-10
Authors: Dinesh Khanna; Daniel E Furst; Philip J Clements; Yannick Allanore; Murray Baron; Lazlo Czirjak; Oliver Distler; Ivan Foeldvari; Masataka Kuwana; Marco Matucci-Cerinic; Maureen Mayes; Thomas Medsger; Peter A Merkel; Janet E Pope; James R Seibold; Virginia Steen; Wendy Stevens; Christopher P Denton Journal: J Scleroderma Relat Disord Date: 2017 Jan-Apr