C103-04 Long-term Efficacy and Safety of Upfront Combination Therapy With Nintedanib and Anti-inflammatory Agents in Treatment-naïve Progressive Pulmonary Fibrosis: TOP-ILD

Background Progressive pulmonary fibrosis (PPF) is a chronic interstitial lung disease characterized by fibrotic progression and poor prognosis. The optimal timing and combination of anti-inflammatory and antifibrotic therapies remain unclear. We previously conducted a multicenter, single-arm phase II trial investigating upfront combination therapy with corticosteroids, tacrolimus, and nintedanib in treatment-naïve PPF patients. At 24 weeks, the primary endpoint demonstrated favorable effects with improvement in the relative forced vital capacity % predicted (%FVC) decline slope from -20.9%/year before treatment to + 11.2%/year after treatment. However, long-term efficacy and safety data beyond 24 weeks are lacking. Objective To evaluate the 52-week efficacy and safety of upfront combination therapy with anti-inflammatory and antifibrotic agents in previously untreated PPF patients. Methods This multicenter, single-arm phase II trial enrolled 34 patients with treatment-naïve PPF, including unclassifiable idiopathic interstitial pneumonia, idiopathic nonspecific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, and rheumatoid arthritis-associated interstitial lung disease. Tacrolimus (0.0375 mg/kg twice daily) and prednisolone (10 mg once daily) were initiated on day 1, with nintedanib (150 mg twice daily) added on day 8. Tacrolimus dosage was adjusted to maintain appropriate blood trough levels. Efficacy, treatment continuation rates, overall survival, and acute exacerbation incidence were evaluated at 52 weeks. Results Enrollment began in April 2023. Protocol treatment maintained improvement in the relative %FVC decline slope from -20.9%/year before treatment to + 2.8%/year at 52 weeks. The relative change in %FVC at 52 weeks was +1.8 ± 21.1%. Treatment continuation rates at week 52 were 87.9% for nintedanib and 91.2% for anti-inflammatory therapy. One-year survival rate was 93.9%, with an acute exacerbation incidence of 3.0% per year. Adverse events included gastrointestinal toxicity (41.2%), glucose intolerance (41.2%), hepatic dysfunction (29.4%), and infections (26.5%), all of which were manageable without treatment discontinuation. Conclusions Upfront combination therapy with tacrolimus, prednisolone, and nintedanib for treatment-naïve PPF maintained high continuation rates and demonstrated favorable long-term outcomes with sustained improvement in pulmonary function. This regimen shows promise as an initial treatment strategy for PPF, warranting validation in larger randomized controlled trials. This abstract is funded by: the Kakihara Foundation