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

Our plain-English summary of Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases, by S.E. Torrisi, N. Kahn, J. Wälscher, et al (BMC Pulmonary Medicine, 2019).

The study

• Authors: S.E. Torrisi, N. Kahn, J. Wälscher, N. Sarmand, M. Polke, K. Lars, M. Eichinger, C.P. Heussel, S. Palmucci, F.M. Sambataro, G. Sambataro, D. Sambataro, C. Vancheri, M. Kreuter
• Journal: BMC Pulmonary Medicine
• Published: 2019;19(1):213
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This retrospective study reviewed records at one specialist lung-disease center in Germany. It covered 11 patients with fibrosing lung diseases other than idiopathic pulmonary fibrosis whose lung function kept declining between October 2014 and January 2018 despite corticosteroids and/or immune-suppressing drugs. One of the 11 had asbestos-related interstitial lung disease. A table gives that patient's baseline lung function, but the article gives no separate results after treatment and no asbestos-specific exposure history. Ten patients received the antifibrotic drug pirfenidone and one received nintedanib. Median FVC (breathing capacity, as percent of predicted) was 56%, 56% and 50% at 24, 12 and 6 months before treatment, 44% at the start, and 46.5% six months later. The decline before treatment was statistically significant. The change after treatment was not (p = 0.17). Only eight patients were measured at that point, because three had died of respiratory failure. Two patients needed lower doses. Median survival was 11.1 months after starting treatment. The authors concluded that antifibrotic treatment may be a valuable option when no other treatment exists. They called randomized trials urgently needed and noted the very small, uncontrolled sample.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective, single-center analysis of patients treated with antifibrotic drugs (case series, no control group)
• Who was studied: 11 patients (8 male, 3 female) at a tertiary referral center for interstitial lung diseases in Germany. All had fibrosing non-IPF interstitial lung diseases that progressed during corticosteroid and/or immunomodulator treatment, October 2014 to January 2018.
• Exposure: Treatment with antifibrotic drugs: pirfenidone 2403 mg per day (10 patients) or nintedanib 300 mg per day (1 patient). Asbestos was relevant only as the diagnosis of one patient (asbestos-associated fibrosis). The per-patient table's 'ILD relevant exposure' row appears to list cement powders for that patient. No fiber type or asbestos-specific exposure history was given.
• Main results:
  • Diagnoses among the 11 patients: unclassifiable ILD in 6, pleuroparenchymal fibroelastosis in 2, idiopathic NSIP in 1, asbestos-related ILD in 1, and Hermansky-Pudlak syndrome in 1.
  • For the patient with asbestos-associated fibrosis (case 8 in Table 2), baseline FVC was 3.37 L (97.7% predicted). No separate post-treatment outcome is reported for this patient.
  • Median FVC (% predicted) for the group was 56%, 56% and 50% at 24, 12 and 6 months before antifibrotic initiation, 44% at initiation, and 46.5% at 6 months after initiation.
  • The FVC change between initiation and 6 months after was not statistically significant (p = 0.17). This comparison used only eight patients, because three died before 6 months due to respiratory failure.
  • Three patients died of respiratory failure before the 6-month follow-up after starting antifibrotics.
  • Dose reduction was needed in 2 patients on pirfenidone, one for rash and one for nausea. Treatment ended early in 3 cases because of death following respiratory failure.
  • Median survival time was 11.1 months from the start of antifibrotic treatment.
• The authors' conclusion: The authors concluded that antifibrotic treatment may be a valuable option for patients with progressive fibrosing non-IPF ILD who do not benefit from corticosteroids and immunosuppressive treatment, if no other options exist. They added that prospective randomized trials are urgently needed.
• Limitations the authors state:
  • Retrospective, single-center study, which may have caused selection bias and missing data.
  • Very small number of patients, so results must be considered with caution and confirmed by trials.
  • The statistical approach was very simple, limited to comparing median FVC before and after antifibrotics.
  • No comparison with an untreated control group was possible, and no quality-of-life data were collected.

Topics

Medical terms in this study, explained in our Lexicon: Interstitial Lung Disease, Idiopathic, Pulmonary Fibrosis, Inflammation, Fibrosis, Multidisciplinary Team, Diffusing Capacity (DLCO), Clinical Trial.

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• Antifibrotic treatment response and prognostic predictors in patients with idiopathic pulmonary fibrosis and exposed to occupational dust — V. Casillo, S. Cerri, et al. (2019)
• Incidence of interstitial lung disease in patients with mesothelioma in the west part of Japan — S. Nojiri, K. Gemba, et al. (2011)
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• Interstitial Lung Diseases in Developing Countries — P. Rivera-Ortega, M. Molina-Molina (2019)

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