Results
Subjects
- Of 663 subjects, 75 (11.3%) had FVC ≤50% predicted; 314 (47.4%) had FVC >50%–≤70% predicted and 274 (41.3%) had FVC >70% predicted at baseline.
Baseline characteristics in subgroups by FVC % predicted
Mean (SD) or % of subjects.
Rate of decline in FVC (mL/year) over 52 weeks by FVC % predicted at baseline in the overall population
- In the placebo group, the mean rate of decline in FVC over 52 weeks was numerically greater in subjects with FVC ≤50% predicted at baseline than in the other subgroups (Figure 1; Figure 2).
- The effect of nintedanib versus placebo on reducing the rate of decline in FVC was numerically more pronounced in subjects with FVC >70% predicted at baseline, but the interaction p-value did not indicate a heterogeneous treatment effect of nintedanib across the subgroups (p=0.75) (Figure 1).
Figure 1. Rate of decline in FVC (mL/year) over 52 weeks in the overall population in subgroups by FVC % predicted at baseline
Treatment-by-subgroup-by-time interaction p=0.75.
Figure 2. Observed change from baseline in FVC (mL) in the overall population in subgroups by FVC % predicted at baseline
Rate of decline in FVC (mL/year) over 52 weeks by FVC % predicted at baseline in subjects with a UIP-like fibrotic pattern on HRCT
- In the placebo group, the mean rate of decline in FVC over 52 weeks was numerically greater in subjects with greater impairment in FVC (Figure 3; Figure 4).
- The effect of nintedanib versus placebo on reducing the rate of decline in FVC was numerically more pronounced in subjects with FVC >70% predicted at baseline, but the interaction p-value did not indicate a heterogeneous treatment effect of nintedanib across the subgroups (p=0.76) (Figure 3).
Figure 3. Rate of decline in FVC (mL/year) over 52 weeks in subjects with UIP-like fibrotic pattern on HRCT in subgroups by FVC % predicted at baseline
Treatment-by-subgroup-by-time interaction p=0.76.
Figure 4. Observed change from baseline in FVC (mL) in subjects with UIP-like fibrotic pattern on HRCT in subgroups by FVC % predicted at baseline
Adverse events
- The adverse event profile of nintedanib was generally consistent across the subgroups by FVC % predicted at baseline, but serious and fatal adverse events were reported in greater proportions of subjects who had FVC <50% predicted at baseline, reflecting their greater disease severity (Figures 5 and 6).
Figure 5. Adverse events (reported irrespective of causality) in subgroups by FVC % predicted at baseline
Data are % of subjects with ≥1 such adverse event reported over 52 weeks (or until 28 days after last trial drug intake in subjects who discontinued trial drug before week 52). *Adverse events that resulted in death, were life threatening, resulted in hospitalisation or prolongation of hospitalisation, resulted in persistent or clinically significant disability or incapacity, were a congenital anomaly or birth defect, or were deemed to be serious for any other reason.
Figure 6. Most frequent gastrointestinal, weight loss and hepatic adverse events (reported irrespective of causality) in subgroups by FVC % predicted at baseline
Gastrointestinal, weight loss and liver enzyme adverse events were coded using preferred terms in the Medical Dictionary for Regulatory Activities. Data are % of subjects with ≥1 such adverse event reported over 52 weeks (or until 28 days after last trial drug intake in subjects who discontinued trial drug before week 52). Adverse events reported in >10% of subjects in either the nintedanib or placebo group in the overall population are shown.