Real-world multicenter prospective study of combination therapy of anti-fibrotic agents in idiopathic pulmonary fibrosis (j-avengers): interim analysis

SESSION TITLE: Diffuse Lung Disease Posters 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown cause and fatal disease, associated with a poor prognosis and a median survival period of three to five years. A conditional recommendation was made for anti-fibrotic agents (nintedanib and pirfenidone) for treatment of IPF in an official American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association clinical practice guideline. Although nintedanib and pirfenidone were demonstrated to slow the progression of IPF, the disease continues to progress. More data is needed on the efficacy of combination therapy with nintedanib and add-on pirfenidone. Therefore, a multicenter prospective observational study investigating the efficacy of combination therapy with nintedanib and add-on pirfenidone was conducted. METHODS: This study is being conducted at the Department of Respiratory Medicine at the Japanese Red Cross Medical Center, JR Tokyo General Hospital, and Toho University Omori Medical Center from December 2019. The primary endpoint was the proportion of patients whose annual decline in FVC was >10%. Patient inclusion criteria were as follows: (1) Patients diagnosed with IPF according to the clinical practice guidelines of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association; (2) patients with IPF aged =40 years who are treated with nintedanib with 50% of FVC or more and =30% of diffusion capacity of the lung for carbon monoxide; and (3) patients with IPF who consent to be treated with nintedanib and add-on pirfenidone. Patient exclusion criteria were as follows: (1) Patients whose forced expiratory volume in 1 second/FVC ratio was <0.7; (2) patients with IPF who have been treated with combination therapy with nintedanib and pirfenidone; (3) patients who require fibrinolysis, full-dose therapeutic anticoagulation, or high-dose antiplatelet therapy; (4) patients who have a history of IPF acute exacerbation within six months, severe unstable comorbidities, including unstable angina, congestive heart failure, or severe bronchial asthma; and (5) patients who were pregnant. RESULTS: Eleven patients (10 men and one woman; median age, 70) were included in February 2023. Baseline characteristics were as follows: Krebs von den Lungen-6, 805 U/mL (304–1568); surfactant protein D, 153 ng/mL (78.9–303); VC, 2.52 L (2.26–3.53); %VC, 72.7% (56.9–83.6); FVC, 2.44 L (2.12–3.63); %FVC, 76.5% (57.2–83.3); and diffusion capacity of the lung for carbon monoxide, 57.2% (36.4–122.1). Among four patients whose time course of pulmonary function testing was able to be evaluated, the decline in FVC was 135 mL/year before and 70 mL/year after 48 weeks after initiation of combination therapy. The decline in %FVC was within 10% in the four patients. CONCLUSIONS: Combination therapy with nintedanib and add-on pirfenidone might reduce the progression of the disease as reflected by lung function in patients with IPF. CLINICAL IMPLICATIONS: There is little evidence of the efficacy of nintedanib with add-on pirfenidone; therefore, combination therapy tends to be stopped despite a slight deterioration of gastrointestinal adverse events like diarrhea and nausea. Further enrollment of patients is needed to evaluate the efficacy of nintedanib with add-on pirfenidone in patients with IPF. DISCLOSURES: No relevant relationships by Nobuyasu Awano No relevant relationships by HARUKA CHIN No relevant relationships by Kazushi Fujimoto No relevant relationships by Minoru Inomata No relevant relationships by Takuma Isshiki No relevant relationships by Yu Ito No relevant relationships by Takehiro Izumo Speaker/Speaker's Bureau relationship with Shionogi Please note: 2021-2023 Added 03/28/2023 by Kazuma Kishi, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehlinger Ingelheim Please note: 2021-2022 Added 03/28/2023 by Kazuma Kishi, source=Web Response, value=Honoraria Advisory Committee Member relationship with Shionogi Please note: 2021-2023 Added 03/29/2023 by Kazuma Kishi, source=Web Response, value=Honoraria Removed 03/29/2023 by Kazuma Kishi, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2021-2023 Added 03/28/2023 by Kazuma Kishi, source=Web Response, value=Grant/Research Support Removed 03/29/2023 by Kazuma Kishi, source=Web Response No relevant relationships by Naoyuki Kuse No relevant relationships by Yutaka Muto No relevant relationships by Yasuhiko Nakamura No relevant relationships by KEITA SAKAMOTO No relevant relationships by Kensuke Tanaka No relevant relationships by Hiroki Umezawa