Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598499
Posterbegehung – Sektion Klinische Pneumologie
Interstitielle Lungenerkrankungen – Ulrich Costabel/Essen, Lars Hagmeyer/Solingen
Georg Thieme Verlag KG Stuttgart · New York

Dose modifications and dose intensity during treatment with pirfenidone

U Costabel
1  Interstitielle und Seltene Lungenkrankheiten, Interstitial and Rare Lung Disease Unit, Ruhrlandklinik
,
SD Nathan
2  Inova Fairfax Hospital
,
L Lancaster
3  Vanderbilt University Medical Center
,
C Albera
4  University of Torino
,
MK Glassberg
5  University of Miami School of Medicine
,
JJ Swigris
6  National Jewish Health
,
F Gilberg
7  Roche
,
KU Kirchgaessler
7  Roche
,
U Petzinger
8  Accovion GmbH
,
PW Noble
9  Cedars-Sinai Medical Center
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)

 

Background:

During treatment of idiopathic pulmonary fibrosis with pirfenidone (PFD), gastrointestinal and skin-related adverse drug reactions (ADR) occurred in ≈30% of patients (pts). Temporary dose reductions and interruptions may allow pts to better manage side effects and continue PFD.

Objective:

To evaluate PFD reductions and interruptions in the Phase 3 CAPACITY and ASCEND trials. Methods:

Pts (623 PFD 2403 mg/day, 624 placebo [PBO]) were followed over 52 weeks. Descriptive statistics and a linear slope analysis for annual rate of decline in forced vital capacity (FVC) by dose intensity were performed.

Results:

Mean daily dose was 2105 mg (median, 2300 mg). Dose reductions and interruptions occurred in 46% and 41% of PFD pts vs. 29% and 25% of PBO pts, respectively. Median duration of reductions and interruptions for PFD pts were 28 and 14 days, respectively. Median time from start of PFD to first dose adjustment for common AEs was ≈95 days except for vomiting (28 days). Dose intensity of > 90% was observed in 424/623 PFD and 559/624 PBO pts. The mean difference (± SEM) in annual rate of FVC decline between PFD and PBO over 52 weeks was 105.5 ± 18.4 mL for dose intensity > 90% (P< 0.0001) and 102.1 ± 43.4 mL for ≤90% (P= 0.0191; Figure).

Zoom Image
Fig. 1: Forced Vital Capacity Volume With Linear Slope Versus Time by Dose Intensity ≤ and > 90% (Based on Actual Dose) – (MITT Population)
FVC, forced vital capacity.
Note: For missing values no imputation was made. Months 3, 6. 9 and 12 correspond to weeks 12, 24, 36 and 48 for the CAPACITY 004 and CAPACITY 006 studies and weeks 13, 26, 39 and 52 for the ASCEND study. Calculated from the mixed linear model comparing pirfenidone 2403 mg/d to placebo, with change from baseline as the outcome variable. Study (CAPACITY 004, CAPACITY 006 and ASCEND), treatment, sex, age and height were fixed effects, whereas subject and assessment time were random effects in an unstructured variance–covariance matrix.

Conclusions:

While PFD dose adjustments may be required to manage ADRs, they tended to occur early and were limited in duration, allowing most pts to maintain efficacy and a high dose intensity.