C103-08 Effect of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis (IPF) by Time Since Diagnosis: Subgroup Analysis of the FIBRONEER-IPF Trial

Abstract Rationale In the FIBRONEER-IPF trial, nerandomilast 9 mg bid and 18 mg bid slowed disease progression in patients with IPF, with a significant reduction in decline in FVC (mL) at week 52 versus placebo (the primary endpoint). Here, we assessed the effect of nerandomilast in subgroups by time since diagnosis of IPF. 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 IPF, hospitalization for respiratory cause, or death up to the final database lock in subgroups defined by time since diagnosis of IPF at baseline. Treatment-by-subgroup interaction p-values were calculated to assess potential heterogeneity in the effect of nerandomilast versus placebo across subgroups. Results At baseline, time since diagnosis of IPF was ≤1 year for 185 patients (15.7%), 1 to ≤ 3 years for 409 patients (34.7%), 3 to ≤ 5 years for 307 patients (26.1%), and 5 years for 276 patients (23.4%). Interaction p-values indicated that there was no evidence of heterogeneity in the effect of nerandomilast versus placebo on change in FVC (mL) at week 52 in subgroups by time since diagnosis of IPF (interaction p = 0.35 for nerandomilast 9 mg bid and p = 0.09 for nerandomilast 18 mg bid) (Figure). However, the effect of nerandomilast was numerically largest in patients with the shortest time since IPF diagnosis (≤1 year). Up to the final database lock, mean (SD) exposure to trial medication was 14.8 (5.1) months. Compared with placebo, the hazard ratios (95% CI) for the composite outcome with nerandomilast 9 mg bid and nerandomilast 18 mg bid, respectively, were 0.81 (0.38, 1.75) and 1.00 (0.47, 2.11) among patients with time since diagnosis ≤1 year, 0.85 (0.51, 1.41) and 1.00 (0.61, 1.65) among patients with time since diagnosis 1 to ≤ 3 years, 1.04 (0.59, 1.85) and 1.05 (0.59, 1.87) among patients with time since diagnosis 3 to ≤ 5 years, and 0.95 (0.57, 1.60) and 0.94 (0.57, 1.57) among patients with time since diagnosis 5 years (interaction p = 0.94 and p = 1.00 for nerandomilast 9 mg bid and 18 mg bid, respectively). Conclusions In the FIBRONEER-IPF trial, nerandomilast slowed disease progression across subgroups by time since diagnosis of IPF, with the numerically largest effect in patients with a time since diagnosis of IPF of ≤ 1 year. Further analyses are needed to understand differences in patient characteristics in subgroups by time since diagnosis. This abstract is funded by: The FIBRONEER-IPF trial was supported by Boehringer Ingelheim.