Possible Value of Antifibrotic Drugs in Patients With Progressive Fibrosing Non-IPF Interstitial Lung Diseases

Sebastiano Emanuele Torrisi; Nicolas Kahn; Julia Wälscher; Nilab Sarmand; Markus Polke; Kehler Lars; Monika Eichinger; Claus Peter Heussel; Stefano Palmucci; Francesca Maria Sambataro; Gianluca Sambataro; Domenico Sambataro; Carlo Vancheri; Michael Kreuter


BMC Pulm Med. 2019;19(213) 

In This Article


Study Population

A retrospective analysis of the database of our tertiary referral Center identified all patients with a multidisciplinary team (MDT) diagnosis of fibrosing non-IPF ILDs that experienced a progressive decline in lung function during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018. At the time of diagnosis, a complete evaluation of medical history, serological data including autoantibodies, all comorbidities and related treatments were assessed. A rheumatologic evaluation was also required to interpret any rheumatologic sign and serological data.[1,22–24] Each patient underwent high resolution computed tomography (HRCT) exams at baseline time and on follow-up every 6–12 months. In-house software YACTA was used to automatically quantify lung density histogram. Longitudinal changes in the 40th and 80th percentiles of attenuation histogram were assessed.[25] If possible, Bronchoalveolar lavage (BAL) and transbronchial cryobiopsy were also performed. Age, physiology and distinct comorbidities were used to calculate the TORVAN index, an index predictive of mortality recently validated for IPF.[26] Patients were considered to have a progressive phenotype if there was evidence of any of the following criteria: a relative decline of ≥10% in forced vital capacity (FVC); a relative decline of ≥15% in diffusing capacity of the lung for carbon monoxide (DLCO); or worsening symptoms or a worsening radiological appearance accompanied by a ≥5–< 10% relative decrease in FVC within a 24-month period prior to antifibrotic therapy initiation.[5,6] Patients underwent routinely follow-up visits and pulmonary function tests (FVC and DLCO) every 6 ± 1 months. Antifibrotic therapy, either pirfenidone or nintedanib, was introduced after a proven progression of the disease and lack of response to corticosteroids and/or immunomodulators, after approval of the respective health insurance company and according to German laws for off-label use and after consent by the patient. As in IPF patients, pirfenidone was given as continuous oral treatment at a dose of 2403 mg·day− 1 (3 capsules three times·day− 1) and nintedanib 300 mg·day− 1 (1 capsule twice·day− 1).[12–17] Patients under antifibrotic therapy were reevaluated every 6–12 weeks after initiation according to the standard of care in our department. Liver function monitoring was conducted on a monthly basis. All adverse events (related and not related to treatment), treatment compliance and interruptions for any reason were also recorded at each treatment visit. To assess difference in one-year mortality between PF-ILD and IPF, a comparison with a cohort of 257 IPF patients collected in our center was also performed. All clinical information was obtained from medical records. Pulmonary function tests (FVC and DLCO) were performed according to the ATS/ERS guidelines.

Statistical Analysis

Characteristics of the study population were expressed as median (interquartile range) or as percentage of the relative frequency as appropriated. Wilcoxon test for paired data was used to assess differences in median FVC between each follow-up time. Kaplan-Meier survival analysis was used to assess overall survival. All the statistical analyses were performed using STATA/IC 14.2 version. A p value less than 0.05 was considered significant.