A39-02 Baseline Characteristics of Patients Enrolled in Progression-IPF, a Pragmatic, Open-label, Randomized Trial of Patients With Progressive Disease in Idiopathic Pulmonary Fibrosis

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with poor prognosis. Although antifibrotic therapies such as pirfenidone and nintedanib slow lung function decline, optimal management of patients with progression despite treatment remains undefined. Evidence-based guidance on whether to continue, switch, or combine antifibrotics is lacking. Objective The PROGRESSION-IPF trial evaluates the efficacy and safety of combination therapy with pirfenidone and nintedanib compared with switching to the alternative antifibrotic or continuing current monotherapy in patients with progressive IPF. Here, we present the baseline characteristics of patients enrolled as of October 24, 2025. Methods This pragmatic, multicenter, randomized, open-label trial was approved by the French ethics committee (CPP Est-2) and the national health authority (ANSM). Patients aged ≥50 years with IPF showing progression per INBUILD criteria but within the previous 12 ± 6 months despite antifibrotic therapy were eligible if forced vital capacity (FVC) was ≥45% predicted. Participants had to be on a stable, well-tolerated dose of pirfenidone or nintedanib prescribed as first-line therapy for at least 6 months. Exclusion criteria included prior or current combined use of pirfenidone and nintedanib, previous sequential exposure to both drugs, contraindication to either antifibrotic, emphysema 15% on HRCT, use of immunosuppressants, or prednisone 10 mg/day. Participants were randomized 1:1:1 to receive combination therapy, switch to the alternative antifibrotic, or continue current monotherapy. The primary endpoint is the slope of FVC decline over 24 weeks. Results A total of 247 patients were randomized and treated. The mean (SD) age was 71.6 (7.3) years; 30% had UIP pattern on biopsy; 84.6% were male, 74.1% were former smokers, and 25.9% never smokers. At baseline, 176 patients (71%) were receiving nintedanib and 71 (28.7%) pirfenidone. FVC was 75.3 (16.4) % predicted, and diffusion capacity for carbon monoxide (DLCO) was 39.2 (13.9) % predicted. Six-minute walking distance was 421 (121) m, with SpO2 of 87 (7) %. Thirty patients (12%) were on oxygen therapy at rest and 69 (28%) during exercise. Comorbidities included sleep apnea (47 19%), reflux (75 30%), and ischemic cardiomyopathy (45 18%). Baseline characteristics by antifibrotic use are shown in the Table. Conclusions This pragmatic randomized trial will determine whether combining pirfenidone and nintedanib provides added benefit over switching or continuing monotherapy in progressive IPF. The results will offer evidence-based guidance for treatment decisions in this frequent and clinically challenging scenario. NCT03939520. Hospices Civils de Lyon. Funding: DGOS PHRC-N, French Ministry of Health. This abstract is funded by: PHRC-N from DGOS, France