Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.
BACKGROUND
The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set.


METHODS
We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients.


RESULTS
In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower.


CONCLUSIONS
This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.
Medizinische Klinik I, Klinikum Grosshadern der Ludwig Maximilians-Universität, München, Germany. juergen.behr@med.uni-muenchen.de
Jürgen
J
Behr
Maurits
M
Demedts
Roland
R
Buhl
Ulrich
U
Costabel
Richard P N
RP
Dekhuijzen
Henk M
HM
Jansen
William
W
MacNee
Michiel
M
Thomeer
Benoit
B
Wallaert
Francois
F
Laurent
Andrew G
AG
Nicholson
Eric K
EK
Verbeken
Johny
J
Verschakelen
C D R
CD
Flower
Stefano
S
Petruzzelli
Paul
P
De Vuyst
J M M
JM
van den Bosch
Eulogio
E
Rodriguez-Becerra
Ida
I
Lankhorst
Marco
M
Sardina
Gabrielle
G
Boissard
D000111:Acetylcysteine / Q000627:therapeutic use*; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011241:Prednisone / Q000627:therapeutic use*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D019141:Respiratory System Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D019141:Respiratory System Agents; D001379:Azathioprine; D011241:Prednisone; D000111:Acetylcysteine