Oral cyclophosphamide for active scleroderma lung disease: a decision analysis.
BACKGROUND
Results from the recent Scleroderma Lung Study (SLS) show that oral cyclophosphamide (CYC) is better than placebo in preventing the progression of scleroderma-related interstitial lung disease (SSc-ILD) at 12 mo but is associated with adverse events. Also, the long-term balance of risk and benefit remains unclear.


METHODS
The authors evaluate the risk-benefit tradeoffs using a Markov decision analytic model to project the quality-adjusted life years (QALYs) for strategies of CYC versus no CYC in SSc-ILD. The base case examined a 50-y-old woman with SSc of 1.5 y, SSc-ILD with moderate ventilatory restriction. The authors analyze the decision to treat with 1 y of daily CYC versus no SSc-ILD-specific therapy. Based on 2-y data from the SLS, the authors assume CYC resulted in no survival benefit and only a transient beneficial impact on pulmonary function. They explore the impact of changes in model parameters through sensitivity analyses, including the efficacy of CYC in preventing progression of lung disease and SSc-ILD- related death. Results. In the base-case analysis, CYC-treated patients fared worse, with a small loss of 0.21 QALYs (16.84 v. 17.15). CYC remained inferior across sensitivity analyses for most variables. In analyses assuming a survival benefit with CYC, CYC resulted in a clinically significant gain (18.17 v. 17.15 QALYs).


CONCLUSIONS
CYC therapy for 1 y results in a small loss in QALYs compared with no CYC for SSc-ILD. The lack of a beneficial impact on survival and the transience of CYC's impact on decline in pulmonary function drive this conclusion.
Khanna
Dinesh
D
Division of Rheumatology, School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095, USA. dkhanna@mednet.ucla.edu
Furst
Daniel E
DE
Clements
Philip J
PJ
Tashkin
Donald P
DP
Eckman
Mark H
MH
D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008390:Markov Chains; D008875:Middle Aged; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide