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Role of pirfenidone in the management of pulmonary fibrosis.

ABSTRACT: Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antifibrotic agents have demonstrated lessening of lung function decline over time. Pirfenidone has been shown to significantly slow decline in forced vital capacity (FVC) over time and prolong progression-free survival, which led to its licensing by the United States Food and Drug Administration (FDA) in 2014 for the treatment of patients with IPF. However, pirfenidone has been associated with significant side effects, and patients treated with pirfenidone must be carefully monitored. We review recent and ongoing clinical research and experience with pirfenidone as a pharmacologic therapy for patients with IPF, provide a suggested approach to incorporate pirfenidone into a treatment algorithm for patients with IPF, and examine the potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by progressive pulmonary fibrosis.

SUBMITTER: Meyer KC

PROVIDER: S-EPMC5388201 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Role of pirfenidone in the management of pulmonary fibrosis.

Meyer Keith C KC Decker Catherine A CA

Therapeutics and clinical risk management 20170403

Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antif ...[more]

PMID: 28435277

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Project description:Background: Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist-physician collaborative management, for patients receiving pirfenidone. Methods: We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist-physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis. Results: In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08-0.96, p = 0.041] and predicted baseline forced vital capacity <60% (HR 2.13, 95% CI 1.17-3.85, p = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (p = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03-0.84, p = 0.027). Conclusions: We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.

Project description:IntroductionPirfenidone is an oral antifibrotic agent approved for idiopathic pulmonary fibrosis (IPF). Real-world data on adverse event (AE) management for pirfenidone are limited. Strategies for managing potential antifibrotic therapy AEs were examined in a sample of US pulmonologists.MethodsAn online, self-administered survey was fielded to pulmonologists between April 10 and May 17, 2017. Pulmonologists were included if they spent > 20% of their time in direct patient care and had ≥ 5 patients with IPF on antifibrotic therapy. Participants answered questions regarding initiation of pirfenidone, dose titration, and management of potential AEs.ResultsA total of 169 pulmonologists participated. Gastrointestinal (GI) intolerance was the most important factor in implementing alternative titration schedules for pirfenidone. Approximately three-quarters of pulmonologists recommended the standard titration scheme for starting treatment; however, a range of titration schedules up to 8 weeks were described, with a 4-week schedule being most common. Pulmonologists reported that most patients treated with alternative titration schedules could achieve the full dose of pirfenidone. Pulmonologists who were most effective at mitigating pirfenidone-related GI AEs by advising dosing at mealtimes more frequently recommended taking pirfenidone during a substantial meal than pulmonologists who were less effective. For photosensitivity AEs, pulmonologists recommended sunscreen use, sun avoidance, wearing a hat, and ultraviolet protection factor clothing.ConclusionsPulmonologists reported that alternative titration schedules for initiating pirfenidone were common and can aid in maintaining the full dose. Proposed strategies to ameliorate pirfenidone-related GI and photosensitivity AEs included taking pirfenidone during a substantial meal and minimizing sun exposure, respectively.FundingF. Hoffmann-La Roche Ltd./Genentech, Inc. Plain language summary available for this article.

Project description:Idiopathic pulmonary fibrosis (IPF) lacks effective treatment. Pirfenidone has been used to treat IPF patients. N-acetylcysteine (NAC) exerts antioxidant and antifibrotic effects on IPF cases.This study is a double-blind, modified placebo-controlled, randomized phase II trial of pirfenidone in Chinese IPF patients. We randomly assigned the enrolled Chinese IPF patients with mild to moderate impairment of pulmonary function to receive either oral pirfenidone (1800 mg per day) and NAC (1800 mg per day) or placebo and NAC (1800 mg per day) for 48 weeks. The primary endpoints were the changes in forced vital capacity (FVC) and walking distance and the lowest SPO2 during the 6-minute walk test (6MWT) at week 48. The key secondary endpoint was the progression-free survival time. This study is registered in ClinicalTrials.gov as number NCT01504334.Eighty-six patients were screened, and 76 cases were enrolled (pirfenidone + NAC: 38; placebo + NAC: 38). The effect of pirfenidone treatment was significant at the 24th week, but this effect did not persist to the 48th week. At the 24th week, the mean decline in both FVC and ?SPO2 (%) during the 6MWT in the pirfenidone group was lower than that in the control group (-0.08 ± 0.20 L vs -0.22 ± 0.29 L, P = 0.02 and -3.44% ± 4.51% vs -6.29% ± 6.06%, P = 0.03, respectively). However, there was no significant difference between these 2 groups at the 48th week (-0.15 ± 0.25 L vs -0.25 ± 0.28 L, P = 0.11 and -4.25% ± 7.27% vs -5.31% ± 5.49%, P = 0.51, respectively). The pirfenidone treatment group did not achieve the maximal distance difference on the 6MWT at either the 24th or the 48th week. But pirfenidone treatment prolonged the progression-free survival time in the IPF patients (hazard ratio = 1.88, 95% confidence interval: 1.092-3.242, P = 0.02). In the pirfenidone group, the adverse event (AE) rate (52.63%) was higher than that in the control group (26.3%, P = 0.03). Rash was more common in the pirfenidone group (39.5% vs 13.2%, P = 0.02).Compared with placebo combined with high-dose NAC, pirfenidone combined with high-dose NAC prolonged the progression-free survival of Chinese IPF patients with mild to moderate impairment of pulmonary function. (ClinicalTrials.gov number, NCT01504334).

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Role of pirfenidone in the management of pulmonary fibrosis.

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Role of pirfenidone in the management of pulmonary fibrosis.

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