Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases

BMC Pulm Med. 2019 Nov 12;19(1):213. doi: 10.1186/s12890-019-0937-0.


Background: Fibrosing, non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases (fILDs) are a heterogeneous group of diseases characterized by a different amount of inflammation and fibrosis. Therapy is currently based on corticosteroids and/or immunomodulators. However, response to these therapies is highly variable, sometimes without meaningful improvement, especially in more fibrosing forms. Pirfenidone and nintedanib have recently demonstrated to reduce functional decline in patients with IPF. However, their antifibrotic mechanism makes these two drugs an interesting approach for treatment of fibrosing ILDs other than IPF.

Objectives: We here report our experience with antifibrotic drugs in fibrosing non-IPF ILDs patients having a progressive phenotype during immunosuppressive therapy.

Methods: Patients with a multidisciplinary team diagnosis of fibrosing non-IPF ILDs experiencing a progressive phenotype during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018 at our tertiary referral Center for ILDs were retrospectively analyzed. Antifibrotic therapy was administered after application with the respective health insurance company and after consent by the patient. Pulmonary-function-tests and follow-up visits were performed every 6 ± 1 months.

Results: Eleven patients were treated with antifibrotic drugs (8 males, mean age 62 ± 12.8 years, mean FVC% 62.8 ± 22.3, mean DLCO% 35.5 ± 10.7, median follow-up under antifibrotic treatment 11.1 months). Patients had a diagnosis of unclassifiable ILD in 6 cases, pleuroparenchymal fibroelastosis in 2 cases, idiopathic-NSIP in 1 case, asbestos-related ILD in 1 case and Hermansky-Pudlak syndrome in 1 case. Treatment before antifibrotics consisted of corticosteroids in all patients: 5 combined with Azathioprin, 1 with either methotrexate or cyclophosphamide (i.v.). Ten patients were treated with pirfenidone (2403 mg/die) and 1 with nintedanib (300 mg/die). Median FVC was 56, 56, 50%, at time points - 24, - 12, - 6 before initiation, 44% at time of initiation and 46.5% at 6 months after initiation of antifibrotic treatment. Antifibrotic treatment was generally well tolerated with a need of dose reduction in 2 cases (rash and nausea) and early termination in 3 cases.

Conclusions: Antifibrotic treatment may be a valuable treatment option in patients with progressive fibrosing non-IPF ILD if currently no other treatment options exist. However, prospective, randomized clinical trials are urgently needed to assess the real impact of antifibrotic therapy in these patients.

Keywords: IPAF; Interstitial lung disease; Nintedanib; Pirfenidone; Progressive fibrosing interstitial lung diseases; Real-world experience.

MeSH terms

  • Aged
  • Disease Progression
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Lung / diagnostic imaging
  • Lung / physiopathology
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Middle Aged
  • Phenotype
  • Pulmonary Fibrosis / diagnostic imaging
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / physiopathology
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Retrospective Studies
  • Risk Factors
  • Tertiary Care Centers
  • Tomography, X-Ray Computed


  • Indoles
  • Pyridones
  • pirfenidone
  • nintedanib