Efficacy and safety of nerandomilast in patients with autoimmune disease-related progressive pulmonary fibrosis in the FIBRONEER-ILD trial.

Methods

Patients with PPF were randomised to receive nerandomilast 9 mg twice a day, nerandomilast 18 mg twice a day, or placebo.

PPF患者被随机分配接受nerandomilast 9 mg每日两次，nerandomilast 18 mg每日两次，或安慰剂。

Among patients with autoimmune ILDs, we evaluated the change in forced vital capacity (FVC) at week 52, and time-to-event endpoints and adverse events over the whole trial.

在自身免疫性疾病相关间质性肺病患者中，我们评估了第52周时用力肺活量(FVC)的变化，以及整个试验期间的事件时间终点和不良事件。

Results

Among 325 patients with autoimmune ILDs, adjusted mean (SE) changes in FVC (mL) at week 52 were -107.1 (25.0) in the placebo group, -61.2 (23.3) in the nerandomilast 9 mg twice a day group (difference vs placebo: 45.9 [95% CI: -20.8 to 112.6]), and -64.9 (23.5) in the nerandomilast 18 mg twice a day group (difference vs placebo: 42.2 [-24.9, 109.3]).

在325名自身免疫性疾病相关间质性肺病患者中，第52周时调整平均(SE)FVC变化(mL)分别为安慰剂组-107.1(25.0)，nerandomilast 9 mg每日两次组-61.2(23.3)(与安慰剂相比差异：45.9[95% CI: -20.8至112.6])，以及nerandomilast 18 mg每日两次组-64.9(23.5)(与安慰剂相比差异：42.2[-24.9, 109.3])。

Over the whole trial (mean exposure to trial medication: 15.8 months), the hazard ratio(HR) vs placebo for time to first acute exacerbation of ILD, hospitalisation for respiratory cause, or death was 0.66 (95% CI: 0.40-1.10) for nerandomilast 9 mg twice a day and 0.56 (0.33-0.94) for nerandomilast 18 mg twice a day, and the HR for time to death was 0.40 (0.17-0.94) for nerandomilast 9 mg twice a day and 0.28 (0.11-0.69) for nerandomilast 18 mg twice a day.

在整个试验期间(平均药物暴露时间为15.8个月)，与安慰剂相比，nerandomilast 9 mg每日两次和nerandomilast 18 mg每日两次的首次急性间质性肺病加重、因呼吸原因住院或死亡的时间风险比(HR)分别为0.66(95% CI: 0.40-1.10)和0.56(0.33-0.94)，死亡时间风险比(HR)分别为0.40(0.17-0.94)和0.28(0.11-0.69)。

Adverse events led to treatment discontinuation in 13.0%, 8.0%, and 10.6% of the placebo, nerandomilast 9 mg twice a day, and nerandomilast 18 mg twice a day groups, respectively.

不良事件导致治疗中断的比例分别为安慰剂组13.0%，nerandomilast 9 mg每日两次组8.0%，nerandomilast 18 mg每日两次组10.6%。

Conclusions

Consistent with the overall trial population, among patients with autoimmune ILDs in FIBRONEER-ILD, nerandomilast slowed progression of pulmonary fibrosis and was well tolerated.

与整个试验人群一致，在FIBRONEER-ILD试验中，nerandomilast减缓了肺纤维化的进展，并且耐受性良好。