Safety and tolerability of pirfenidone in asbestosis: a prospective multicenter study

Our plain-English summary of Safety and tolerability of pirfenidone in asbestosis: a prospective multicenter study, by J.R. Miedema, C.C. Moor, M. Veltkamp, et al (Respiratory Research, 2022).

The study

• Authors: J.R. Miedema, C.C. Moor, M. Veltkamp, S. Baart, N.S.L. Lie, J.C. Grutters, M.S. Wijsenbeek, R.L.M. Mostard
• Journal: Respiratory Research
• Published: 2022;23(1):139
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype.

Methods: This was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements.

Results: In total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant.

Conclusions: Treatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis. Trial registration MEC-2018-1392; EudraCT number: 2018-001781-41.

© 2022. The Author(s).

In plain English

This small study at three Dutch hospitals tested pirfenidone in people with asbestosis and worsening lung function. Ten patients were included between April 2019 and June 2020. All were male former smokers, mean age 74.7 years. The plan was 12 weeks without the drug, then 24 weeks of pirfenidone (maintenance dose 801 mg three times a day). Two patients died, one before starting the drug and one after stopping it, deaths the authors called unrelated to treatment. Patients did daily home breathing tests and weekly online symptom reports. Six patients had adverse events, most often fatigue, rash, anorexia and cough; the article reports this as 66.7%, which matches nine patients, not ten. Six needed a dose reduction, and the authors reported that all could continue after the adjustment. Hospital lung tests, walking distance and questionnaires showed no significant changes. Home tests showed lung volume (FVC) declining significantly before treatment and stable during it, but the two periods did not differ significantly. The authors concluded that pirfenidone was acceptably safe and tolerable and that home data suggest it might slow decline.

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: Small exploratory multicenter prospective study with a single group: a 12-week observation period without the drug, followed by a planned 24 weeks of pirfenidone treatment
• Who was studied: 10 patients with asbestosis and documented progressive lung function decline, at three sites in the Netherlands, included April 2019 to June 2020; all male ex-smokers, mean age 74.7 years (SD 7.2)
• Exposure: The treatment studied was pirfenidone, built up to a maintenance dose of 801 mg three times a day for a planned 24 weeks. Previous asbestos exposure with a proper latency period was an entry criterion; the article does not specify fiber types, products or jobs.
• Main results:
  • 6 patients (66.7%) experienced any intermittent adverse event during the study period. The article does not state the denominator. 66.7% corresponds to 6 of 9 patients, not 6 of the 10 included.
  • Fatigue (55.6%) and rash (44.4%) were the most common self-reported adverse events. Anorexia and cough were each reported by 4 patients (44.4%).
  • Six patients needed a dose reduction because of side effects. The authors state all were able to continue treatment after the (temporary) dose adjustment.
  • No dose adjustments were needed because of abnormal liver tests (aminotransferases, bilirubin) or other laboratory abnormalities
  • Two patients were hospitalized, one for pneumonia and one for angina, which the authors reported as not related to treatment
  • Two patients died. One died of progression of asbestosis during the observation period, before starting pirfenidone. The other died by euthanasia after stopping pirfenidone during the treatment period. The authors reported both deaths as not related to treatment.
  • In the 8 patients with hospital measurements, FVC and DLCO remained stable before and during treatment. The 6-minute walking distance (baseline median 405 m) did not change significantly.
  • Home spirometry was analyzed in 9 patients; the patient who died before treatment was excluded. FVC declined significantly during the observation period (p = 0.047) and remained stable during treatment (p = 0.76). The slopes before and after starting treatment did not differ significantly (p = 0.14).
  • Patient-reported outcome scores did not change significantly during the study. Baseline mean scores were 46.8 on the K-BILD and 14.6 on the Leicester Cough Questionnaire.
• The authors' conclusion: The authors concluded that pirfenidone had an acceptable safety and tolerability profile in asbestosis. They also concluded that home spirometry data suggest it might attenuate FVC decline in progressive asbestosis.
• Limitations the authors state:
  • The main limitation was the planned low number of patients, so the primary safety endpoint could only be described, not formally tested
  • The study was not powered to detect a treatment effect on pulmonary function measurements
  • The authors suggested that adverse event rates higher than in other studies might reflect the active weekly electronic collection of adverse events

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Disease Progression, Idiopathic, Pulmonary Fibrosis, Spirometry, Diffusing Capacity (DLCO).

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