title: Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease.
abstract: 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).
authors: 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
authors: Donald P
authors: DP
authors: Tashkin
authors: Robert
authors: R
authors: Elashoff
authors: Philip J
authors: PJ
authors: Clements
authors: Michael D
authors: MD
authors: Roth
authors: Daniel E
authors: DE
authors: Furst
authors: Richard M
authors: RM
authors: Silver
authors: Jonathan
authors: J
authors: Goldin
authors: Edgar
authors: E
authors: Arriola
authors: Charlie
authors: C
authors: Strange
authors: Marcy B
authors: MB
authors: Bolster
authors: James R
authors: JR
authors: Seibold
authors: David J
authors: DJ
authors: Riley
authors: Vivien M
authors: VM
authors: Hsu
authors: John
authors: J
authors: Varga
authors: Dean
authors: D
authors: Schraufnagel
authors: Arthur
authors: A
authors: Theodore
authors: Robert
authors: R
authors: Simms
authors: Robert
authors: R
authors: Wise
authors: Fred
authors: F
authors: Wigley
authors: Barbara
authors: B
authors: White
authors: Virginia
authors: V
authors: Steen
authors: Charles
authors: C
authors: Read
authors: Maureen
authors: M
authors: Mayes
authors: Ed
authors: E
authors: Parsley
authors: Kamal
authors: K
authors: Mubarak
authors: M Kari
authors: MK
authors: Connolly
authors: Jeffrey
authors: J
authors: Golden
authors: Mitchell
authors: M
authors: Olman
authors: Barri
authors: B
authors: Fessler
authors: Naomi
authors: N
authors: Rothfield
authors: Mark
authors: M
authors: Metersky
authors: Dinesh
authors: D
authors: Khanna
authors: Ning
authors: N
authors: Li
authors: Gang
authors: G
authors: Li
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
references: Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):400-6
references: 8756813
references: Ann Intern Med. 1996 Mar 1;124(5):477-84
references: 8602705
references: J Rheumatol. 1998 Jul;25(7):1325-9
references: 9676764
references: Proc Am Thorac Soc. 2006 May;3(3):234-8
references: 16636091
references: N Engl J Med. 2006 Jun 22;354(25):2655-66
references: 16790698
references: N Engl J Med. 2006 Jun 22;354(25):2707-9
references: 16790705
references: Arthritis Rheum. 2006 Dec;54(12):3962-70
references: 17133610
references: Stat Med. 2007 Jun 30;26(14):2813-35
references: 17124698
references: Arthritis Rheum. 1997 Nov;40(11):1984-91
references: 9365087
references: Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2185-98
references: 8520796
references: BMJ. 2000 May 13;320(7245):1297-303
references: 10807619
references: Ann Intern Med. 2000 Jun 20;132(12):947-54
references: 10858177
references: Arthritis Rheum. 2001 Mar;44(3):653-61
references: 11263780
references: J Allergy Clin Immunol. 2001 Aug;108(2):184-90
references: 11496232
references: Monaldi Arch Chest Dis. 2001 Aug;56(4):325-30
references: 11770215
references: J Rheumatol. 2002 Feb;29(2):298-304
references: 11842824
references: J Rheumatol. 2002 Apr;29(4):731-6
references: 11950014
references: Arthritis Rheum. 1980 May;23(5):581-90
references: 7378088
references: Am Rev Respir Dis. 1981 Feb;123(2):185-9
references: 7235357
references: Am Rev Respir Dis. 1981 Jun;123(6):659-64
references: 7271065
references: Ann Rheum Dis. 1983 Aug;42(4):368-73
references: 6882031
references: Chest. 1984 Jun;85(6):751-8
references: 6723384
references: J Rheumatol. 1993 May;20(5):838-44
references: 8336309
references: Arthritis Rheum. 1994 May;37(5):729-35
references: 8185701
references: Respir Med. 1994 Mar;88(3):165-94
references: 8209067
references: Arthritis Rheum. 1994 Sep;37(9):1283-9
references: 7945490
references: Arthritis Rheum. 1994 Sep;37(9):1290-6
references: 7945491
references: Respir Care. 1994 Dec;39(12):1184-90
references: 10146140
references: Arthritis Rheum. 1995 Aug;38(8):1120-7
references: 7639809
references: Am J Respir Crit Care Med. 1995 Sep;152(3):1107-36
references: 7663792
references: J Rheumatol. 1995 Jul;22(7):1281-5
references: 7562759