In 33 patients with myositis-associated ILD from FIBRONEER-ILD, nerandomilast numerically slowed FVC decline and lowered progression risk.
Nerandomilast FVC and progression outcomes in IIM-ILD
Nerandomilast showed consistent trends toward reduced forced vital capacity (FVC) decline and disease progression in patients with idiopathic inflammatory myopathy–associated interstitial lung disease (IIM-ILD), according to a post hoc subgroup analysis of the phase 3 FIBRONEER-ILD trial presented at the
Nerandomilast is an oral preferential phosphodiesterase 4B (PDE4B) inhibitor, and in the overall FIBRONEER-ILD population of patients with progressive pulmonary fibrosis (PPF), it reduced FVC decline vs placebo over 52 weeks.² Progressive fibrosis can develop in IIM-ILD despite immunosuppression, and the current analysis, led by Rohit Aggarwal, MD, MS, of the University of Pittsburgh, examined the myositis subgroup specifically.¹
FIBRONEER-ILD randomized patients with PPF other than idiopathic pulmonary fibrosis, defined by INBUILD criteria, 1:1:1 to nerandomilast 18 mg twice daily, 9 mg twice daily, or placebo, with stable background nintedanib permitted.¹ The IIM-ILD subgroup included 33 patients, with nine in the 9-mg group and 12 in the 18-mg group.¹
At week 52, the adjusted mean difference in FVC vs placebo was 96.7 mL (95% CI, −78.7 to 272.1) with 9 mg and 133.5 mL (95% CI, −27.0 to 294.0) with 18 mg.¹ The 18-mg dose showed larger FVC differences than the 9-mg dose at all time points.¹
Disease progression and safety with nerandomilast in myositis ILD
For the key secondary composite endpoint of time to first acute ILD exacerbation, respiratory hospitalization, or death, the hazard ratio vs placebo was 0.16 (95% CI, 0.02-0.98) with 9 mg and 0.06 (95% CI, <0.01-0.61) with 18 mg.¹
Background therapy differed across groups, with corticosteroid use in 83.3% of the placebo group, 66.7% of the 9-mg group, and 50.0% of the 18-mg group, and immunosuppressant use in 66.7%, 55.6%, and 33.3%, respectively.¹ Agents including mycophenolate, rituximab, cyclophosphamide, and tocilizumab were excluded at screening but could be started after six months for worsening systemic disease.¹
Safety was generally consistent with the overall trial population, with diarrhea and upper respiratory tract infection the most common adverse events.¹ Diarrhea occurred in 2 patients receiving placebo, 4 receiving 9 mg, and one receiving 18 mg, and all cases were mild or moderate.¹
“These findings, despite the small sample size, suggest that nerandomilast may have therapeutic potential in IIM-ILD,” the investigators wrote.¹
The analysis was post hoc, with wide CIs, imbalanced background immunosuppression favoring the placebo group, and few events in the composite endpoint. The trial was sponsored by Boehringer Ingelheim, six authors are Boehringer Ingelheim employees, and Aggarwal and coauthor Shervin Assassi, MD, MS, report relationships with Boehringer Ingelheim and other companies.¹
