Efficacy and Safety of Nerandomilast in Patients with Autoimmune Disease-Related Progressive Pulmonary Fibrosis: Subgroup Analysis of the FIBRONEER-ILD trial

Anna-Maria Hoffmann-Vold¹, Shervin Assassi², Vincent Cottin³, Michael Kreuter⁴, Claudia Valenzuela⁵, Marlies S Wijsenbeek⁶, Hui Gu⁷, Ivana Ritter⁸, Susanne Stowasser⁸, Gerrit Weimann⁸ and Toby M Maher⁹, ¹Oslo University Hospital, Oslo, Norway, ²Division of Rheumatology, UTHealth Houston, Houston, Texas, USA, Houston, TX, ³National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon ¹, UMR ⁷⁵⁴, ERN-LUNG, Lyon, France, Lyon, France, ⁴Center for Pulmonary Medicine, Department of Pneumology, Mainz University Medical Center and Pulmonary, Critical Care & Sleep Medicine, Marienhaus Clinic Mainz, Mainz, Germany, Heidelberg, Germany, ⁵Pulmonology Department, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain, Madrid, Spain, ⁶Center of Expertise for Interstitial Lung Diseases, Department of Respiratory Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands, Rotterdam, Netherlands, ⁷Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, Ridgefield, ⁸Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim am Rhein, Germany, ⁹Department of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA and Section of Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK, Los Angeles

Meeting: ACR Convergence 2025

Keywords: autoimmune diseases, clinical trial, interstitial lung disease, pulmonary, Randomized Trial

Session Information

Date: Monday, October 27, 2025

Title: Abstracts: Miscellaneous Rheumatic & Inflammatory Diseases II: Models and Mechanisms (1662–1667)

Session Type: Abstract Session

Session Time: 1:00PM-1:15PM

Background/Purpose: Nerandomilast is a preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. The Phase III FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF) showed that nerandomilast significantly reduced the decline in forced vital capacity (FVC) and had an acceptable safety profile. We explored the efficacy and safety of nerandomilast in the subgroup of patients with autoimmune disease-related interstitial lung diseases (ILDs) (autoimmune ILDs) in the FIBRONEER-ILD trial.

Methods: Patients with PPF (excluding idiopathic pulmonary fibrosis) were randomized 1:1:1 to receive nerandomilast 9 mg bid, nerandomilast 18 mg bid, or placebo. PPF was defined using the same criteria as in the INBUILD trial (Flaherty KR et al. N Engl J Med 2019;381:1718-27). Patients taking nintedanib (at a stable dose for ≥12 weeks) or not taking nintedanib (for ≥8 weeks) were eligible to participate. Cyclophosphamide, tocilizumab, mycophenolate, or rituximab were not permitted at enrolment but could be initiated after 6 months to manage worsening systemic disease. Prednisone >15 mg/day (or equivalent) was not permitted at enrolment but could be prescribed during the trial for acute exacerbation of ILD or after 6 months to manage worsening systemic disease. In the subgroup with autoimmune ILDs, we evaluated absolute change from baseline in FVC (mL) at week 52 and adverse events up to week 52. Analyses were pre-specified.

Results: Among 1176 treated patients, 325 (27.6%) had autoimmune ILDs (100 placebo, 112 nerandomilast 9 mg bid, 113 nerandomilast 18 mg bid). At baseline, among patients with autoimmune ILDs, 212 (65.2%) were female, mean (SD) age was 63.4 (11.2) years, FVC was 71.5 (15.0) % predicted, diffusing capacity for carbon monoxide (DLco) was 51.5 (16.8) % predicted; 111 (34.2%) patients were taking nintedanib. The most frequent autoimmune disease diagnoses were rheumatoid arthritis (118 patients [36.3%]), systemic sclerosis (75 [23.1%]), and mixed connective tissue disease (47 [14.5%]). Among patients with autoimmune ILDs, adjusted mean changes in FVC (mL) at week 52 were -107.1 (95% CI: -156.1, -58.0) in the placebo group, -61.2 (-106.9, -15.5) in the nerandomilast 9 mg bid group (difference vs placebo: 45.9 [95% CI: -20.8, 112.6]), and -64.9 (-111.0, -18.7) in the nerandomilast 18 mg bid group (difference vs placebo: 42.2 [-24.9, 109.3]) (Figure). The most frequent adverse event was diarrhea (Table). Adverse events leading to treatment discontinuation were similar across treatment groups.

Conclusion: In the FIBRONEER-ILD trial, the efficacy of nerandomilast on slowing decline in FVC in patients with autoimmune ILDs was consistent with that observed in the overall trial population. Nerandomilast had an acceptable safety and tolerability profile.

Figure. Change from baseline in FVC (mL) at week 52 among patients with autoimmune ILDs in the FIBRONEER-ILD trial.

Table. Adverse events up to week 52 in patients with autoimmune ILDs in the FIBRONEER-ILD trial.

Disclosures: A. Hoffmann-Vold: AbbVie, 2, Avalyn, 2, Boehringer Ingelheim, 2, 5, 6, 12, Medical writing support provided by Fleishman Hillard., Bristol-Myers Squibb, 2, Calluna Pharma, 2, Genentech, 2, Janssen, 2, 5, 6, Medscape, 2, 6, Merck Sharp & Dohme, 2, 6, Novartis, 6, Pliant Therapeutics, 2, Roche, 2, 6, Werfen, 2; S. Assassi: AbbVie, 2, AstraZeneca, 2, aTyr, 2, 5, Boehringer Ingelheim, 2, 5, 6, 12, Medical writing support provided by Fleishman Hillard, CSL Behring, 2, Janssen, 5, Merck, 2, Mitsubishi Tanabe, 2, PeerView Institute for Medical Education, 6, Scleroderma Research Foundation, 5, 6, Takeda, 2, TeneoFour, 2; V. Cottin: AbbVie, 2, AstraZeneca, 2, Avalyn, 2, Boehringer Ingelheim, 2, 6, 12, Support for attending meetings and medical writing support provided by Fleishman Hillard, Bristol-Myers Squibb/Celgene, 2, CSL (Behring/Vifor), 2, Ferrer/United Therapeutics, 2, 6, FibroGen, 12, Adjudication committee, GlaxoSmithKleine, 1, 2, Gossamer, 2, Liquidia, 2, Molecure, 1, Pliant, 2, PureTech, 2, Roche, 2, 6, Roivant, 2, Sanofi, 2, 6, 12, Support for attending meetings, Shionogi, 2; M. Kreuter: AstraZeneca, 2, Boehringer-Ingelheim, 2, 5, 6, 12, Medical writing support provided by Fleishman Hillard, Deutsche Gesellschaft für Pneumologiex, 12, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, European Respiratory Society, 12, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, GlaxoSmithKleine, 2, Roche, 2, 5, 6; C. Valenzuela: Boehringer-Ingelheim, 1, 2, 6, 12, Support for attending meetings and medical writing support provided by Fleishman Hillard, Bristol-Myers Squibb, 2, Ferrer, 2, 6, 12, Support for attending meetings, Pliant, 1, 3; M. Wijsenbeek: AstraZeneca, 2, AstraZeneca/Daiichi, 5, Avalyn Pharma, 2, 6, 12, Support for attending meetings, Boehringer Ingelheim, 2, 5, 6, 12, Support for attending meetings and Marlies Wijsenbeek served as a member of the SC for the FIBRONEER trials which are funded by Boehringer Ingelheim, Bristol-Myers Squibb, 2, CSL Behring, 2, 6, Erasmus MC, 5, Galapagos, 2, Galecto, 2, GlaxoSmithKleine, 2, 12, Support for attending meetings, Hoffmann-La Roche, 2, 5, Horizon Therapeutics, 2, Kinevant Sciences, 2, Molecure, 2, NeRRe Therapeutics, 2, Novartis, 2, PureTech Health, 2, Respivant Science, 2, Sanofi, 2, Sarcoidosis.nl, 5, The Dutch Lung Foundation, 5, The Dutch Pulmonary Fibrosis Patients Association, 5, The Netherlands Organization for Health Research and Development, 5, The Thorax Foundation, 5, Trevi, 2, Vicore, 2; H. Gu: Boehringer Ingelheim, 3, 12, Medical writing support provided by Fleishman Hillard; I. Ritter: Boehringer Ingelheim, 3, 12, Medical writing support provided by Fleishman Hillard; S. Stowasser: Boehringer Ingelheim, 3, 12, Medical writing support provided by Fleishman Hillard; G. Weimann: Boehringer Ingelheim, 3; T. Maher: AbbVie, 2, Amgen, 2, AstraZeneca, 2, 5, Bayer, 2, Biogen Idec, 2, Blade Therapeutics, 2, Boehringer Ingelheim, 2, 6, 12, Medical writing support provided by Fleishman Hillard, Bristol-Myers Squibb, 2, Endeavor BioMedicines, 2, Galapagos NV, 2, Galecto Pharma, 2, GlaxoSmithKline, 2, 5, Gossamer Bio, 2, Merck, 2, Pfizer, 2, Pliant, 2, Redx Pharma, 2, Roche, 2, 6, Three Lakes Partners, 2, Trevi, 2, UCB, 2, 5, United Therapeutics, 2, Vicore Pharma, 2.

To cite this abstract in AMA style:

Hoffmann-Vold A, Assassi S, Cottin V, Kreuter M, Valenzuela C, Wijsenbeek M, Gu H, Ritter I, Stowasser S, Weimann G, Maher T. Efficacy and Safety of Nerandomilast in Patients with Autoimmune Disease-Related Progressive Pulmonary Fibrosis: Subgroup Analysis of the FIBRONEER-ILD trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-nerandomilast-in-patients-with-autoimmune-disease-related-progressive-pulmonary-fibrosis-subgroup-analysis-of-the-fibroneer-ild-trial/. Accessed .

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