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Introduction Nerandomilast, a preferential phosphodiesterase 4B inhibitor with antifibrotic and immunomodulatory properties, significantly reduced forced vital capacity (FVC) decline and was linked to fewer deaths versus placebo with an acceptable safety profile in the Phase III FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF). Outcomes in the subgroup of patients with autoimmune interstitial lung disorders (ILDs) were consistent with those in the overall population. Findings from the subgroup of patients with systemic sclerosis-associated ILD (SSc-ILD) are presented.Material and Methods Patients with PPF (excluding idiopathic pulmonary fibrosis) were randomised 1:1:1 to receive nerandomilast 9 mg twice daily (BID), nerandomilast 18 mg BID, or placebo. PPF was defined using the INBUILD trial criteria. Patients not taking nintedanib (>=8 weeks) or on a stable dose (>=12 weeks) were eligible. Cyclophosphamide, tocilizumab, mycophenolate, or rituximab were not permitted but could be initiated after 6 months for worsening systemic disease. Prednisone >15 mg/day (or equivalent) was not permitted but could be prescribed during the trial for acute ILD exacerbation or after 6 months for worsening systemic disease. A post-hoc subgroup analysis in patients with SSc-ILD was performed.Results Among 1176 treated patients, 325 (27.6%) had autoimmune ILDs; of these, 75 (23.1%) had SSc-ILD (23 placebo, 25 nerandomilast 9 mg BID, 27 nerandomilast 18 mg BID). At baseline, among patients with SSc-ILD, 62 (82.7%) were female; mean (standard deviation [SD]) age was 60.2 (11.8) years; mean FVC % predicted (SD) was 69.42% (13.78); mean diffusing capacity for carbon monoxide % predicted (SD) was 48.99% (15.08); and 38 (50.7%) patients were taking nintedanib. Among patients with SSc-ILD, adjusted mean changes in FVC at Week 52 were –116.13 mL (95% confidence interval [CI]: –220.24, –12.03) in the placebo group, –49.13 mL (–146.31, 48.05) in the nerandomilast 9 mg BID group (difference vs placebo: 67.00 mL [95% CI: –75.31, 209.32]), and 0.54 mL (–93.87, 94.95) in the nerandomilast 18 mg BID group (difference vs placebo: 116.67 mL [95% CI: –23.58, 256.93]). The most frequent adverse event was diarrhoea reported in 4 (17.4%), 7 (28.0%) and 11 (40.7%) patients in the placebo, nerandomilast 9 mg and 18 mg BID groups, respectively. Rates of treatment discontinuation due to adverse events were similar across treatment groups.Conclusions In the FIBRONEER-ILD trial, nerandomilast slowed the decline in FVC and had an acceptable safety and tolerability profile in patients with PPF. This post-hoc subgroup analysis, while underpowered, showed consistent findings in patients with SSc-ILD.