Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease.
BACKGROUND
The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear.


OBJECTIVE
A second year of follow-up was performed to determine if these effects persisted after stopping treatment.


METHODS
A detailed analysis of data obtained over the two years of the study was performed.


RESULTS
Using a longitudinal joint model, we analyzed FVC, total lung capacity, transitional dyspnea index, Rodnan skin scores, and the Health Assessment Questionnaire-Disability Index during the second year, after adjusting for baseline values, baseline fibrosis score, and nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months of therapy and returned at 24 month or had their 24-month data imputed. The beneficial effects of CYC on pulmonary function and health status continued to increase through 18 months, after which they dissipated, whereas skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon.


CONCLUSIONS
One year of CYC improved lung function, skin scores, dyspnea, and health status/disability, effects which either persisted or increased further for several months after stopping therapy. However, except for a sustained impact on dyspnea, all of these effects waned and were no longer apparent at 24 months. Treatment strategies aimed at extending the positive therapeutic effects observed with CYC should be considered. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).
Tashkin
Donald P
DP
Department of Medicine, David Geffen School of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1690, USA. dtashkin@mednet.ucla.edu
Elashoff
Robert
R
Clements
Philip J
PJ
Roth
Michael D
MD
Furst
Daniel E
DE
Silver
Richard M
RM
Goldin
Jonathan
J
Arriola
Edgar
E
Strange
Charlie
C
Bolster
Marcy B
MB
Seibold
James R
JR
Riley
David J
DJ
Hsu
Vivien M
VM
Varga
John
J
Schraufnagel
Dean
D
Theodore
Arthur
A
Simms
Robert
R
Wise
Robert
R
Wigley
Fred
F
White
Barbara
B
Steen
Virginia
V
Read
Charles
C
Mayes
Maureen
M
Parsley
Ed
E
Mubarak
Kamal
K
Connolly
M Kari
MK
Golden
Jeffrey
J
Olman
Mitchell
M
Fessler
Barri
B
Rothfield
Naomi
N
Metersky
Mark
M
Khanna
Dinesh
D
Li
Ning
N
Li
Gang
G
D000284:Administration, Oral; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014109:Total Lung Capacity; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
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