Abstract Rationale In the FIBRONEER-IPF trial in patients with IPF, nerandomilast 9 mg bid and 18 mg bid slowed disease progression, with a significant reduction in decline in FVC (mL) at week 52 versus placebo (the primary endpoint). We assessed the effect of nerandomilast in subgroups by GAP stage at baseline. Methods In post-hoc analyses, we assessed the change from baseline in FVC (mL) at week 52; time to first acute exacerbation of IPF, hospitalization for respiratory cause, or death up to final database lock; and time to death up to final database lock in subgroups by GAP stage at baseline. GAP stage is calculated based on sex, age, FVC % predicted, and DLco % predicted, with a higher GAP stage indicating a higher risk of mortality. Results At baseline, 482 patients (41.0%) were at GAP stage I, 582 (49.4%) at GAP stage II, 107 (9.1%) at GAP stage III, and 6 (0.5%) had missing data on GAP stage. There was no evidence of heterogeneity in the effect of nerandomilast vs placebo on change in FVC (mL) at week 52 in subgroups by GAP stage at baseline (interaction p = 0.56 and p = 0.91 for nerandomilast 9 mg bid and 18 mg bid, respectively) (Figure). Mean (SD) exposure to trial medication was 14.8 (5.1) months. Compared with placebo, the hazard ratios (95% CI) for first acute exacerbation of IPF, hospitalization for respiratory cause, or death with nerandomilast 9 mg bid and nerandomilast 18 mg bid, respectively, were 0.92 (0.51, 1.63) and 0.74 (0.40, 1.38) for patients at GAP stage I, 0.92 (0.63, 1.34) and 1.04 (0.72, 1.49) for patients at GAP stage II, and 0.91 (0.47, 1.79) and 1.32 (0.69, 2.52) for patients at GAP stage III (interaction p = 1.00 and p = 0.45 for nerandomilast 9 mg bid and 18 mg bid, respectively). Compared with placebo, the hazard ratios (95% CI) for death with nerandomilast 9 mg bid and nerandomilast 18 mg bid, respectively, were 0.83 (0.31, 2.24) and 0.42 (0.12, 1.43) for patients at GAP stage I, 1.06 (0.57, 1.96) and 0.74 (0.38, 1.44) for patients at GAP stage II, and 0.69 (0.28, 1.71) and 0.61 (0.24, 1.52) for patients at GAP stage III (interaction p = 0.73 and p = 0.72 for nerandomilast 9 mg bid and 18 mg bid, respectively). Conclusions In the FIBRONEER-IPF trial, nerandomilast slowed disease progression across subgroups based on GAP stage at baseline, including in patients at GAP stage I. This abstract is funded by: The FIBRONEER-IPF trial was supported by Boehringer Ingelheim.
Lee et al. (Fri,) studied this question.