Abstract Rationale In the FIBRONEER-ILD trial in patients with PPF, nerandomilast 9 mg bid and 18 mg bid slowed disease progression, with a significant reduction in the decline in FVC (mL) at week 52 versus placebo (the primary endpoint). We assessed the effect of nerandomilast across subgroups by time since diagnosis of ILD. Methods In post-hoc analyses, we assessed the change from baseline in FVC (mL) at week 52 and the time to first acute exacerbation of ILD, hospitalization for respiratory cause, or death up to the main (first) database lock in subgroups by time since diagnosis of ILD at baseline. Treatment-by-subgroup interaction p-values were calculated to assess potential heterogeneity in the effect of nerandomilast versus placebo across subgroups. Results A total of 1176 patients received trial medication. At baseline, time since diagnosis of ILD was ≤1 year for 212 patients (18.0%), 1 to ≤ 3 years for 399 patients (33.9%), 3 to ≤ 5 years for 215 patients (18.3%), and 5 years for 350 patients (29.8%). There was no evidence of heterogeneity in the effect of nerandomilast versus placebo on change in FVC at week 52 in subgroups by time since diagnosis of ILD (interaction p = 0.64 for nerandomilast 9 mg bid and p = 0.40 for nerandomilast 18 mg bid) (Figure). Mean exposure to trial medication up to the main (first) database lock was 14.4 months. Compared with placebo, the hazard ratios (95% CI) for time to first acute exacerbation of ILD, hospitalization for respiratory cause, or death with nerandomilast 9 mg bid and nerandomilast 18 mg bid, respectively, were 0.83 (0.46, 1.49) and 0.63 (0.33, 1.23) among patients with time since diagnosis ≤1 year, 0.95 (0.61, 1.46) and 0.51 (0.30, 0.87) among patients with time since diagnosis 1 to ≤ 3 years, 0.60 (0.33, 1.11) and 0.74 (0.42, 1.31) among patients with time since diagnosis 3 to ≤ 5 years, and 1.07 (0.64, 1.78) and 1.21 (0.74, 1.99) among patients with time since diagnosis 5 years (interaction p = 0.54 and p = 0.12 for nerandomilast 9 mg bid and 18 mg bid, respectively). Conclusions In the FIBRONEER-ILD trial in patients with PPF, the effect of nerandomilast on slowing ILD progression is consistent across subgroups by time since diagnosis of ILD, including in patients with a time since diagnosis of ILD of ≤ 1 year. This abstract is funded by: The FIBRONEER-ILD trial was supported by Boehringer Ingelheim.
Farrand et al. (Fri,) studied this question.