Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial

Sakamoto, Susumu; Kataoka, Kensuke; Kondoh, Yasuhiro; Kato, Motoyasu; Okamoto, Masaki; Mukae, Hiroshi; Bando, Masashi; Suda, Takafumi; Yatera, Kazuhiro; Tanino, Yoshinori; Kishaba, Tomoo; Hattori, Noboru; Terada, Yoshio; Saito, Takefumi; Nishioka, Yasuhiko; Kuwano, Kazuyoshi; Kishi, Kazuma; Inase, Naohiko; Sasaki, Shin‐ichi; Takizawa, Hajime; Johkoh, Takeshi; Sakai, Fumikazu; Homma, Sakae

doi:10.1183/13993003.00348-2020

Cited by 32 publications

(48 citation statements)

References 26 publications

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“…The baseline FVC per cent predicted was reduced across most studies. Table 1 presents the essential patient characteristics, and online supplemental table 1 has the individual trial characteristics 27 31–65 Online supplemental appendix 3. contains the network estimates for all outcomes.…”

Section: Resultsmentioning

confidence: 99%

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Pitre

Mah

Helmeczi

et al. 2022

Thorax

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments.MethodsWe searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework.ResultsWe identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (–88.35 to 411.12)), pirfenidone (2.47% (–0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty).Conclusion and relevanceFuture guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

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Section: Resultsmentioning

confidence: 99%

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Pitre

Mah

Helmeczi

et al. 2022

Thorax

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“…Furthermore, the combination therapy of nintedanib and sildenafil only has pronounced effects on IPF patients who have right heart dysfunction (RHD) ( Behr et al, 2019 ). Combination treatment with inhaled N-acetylcysteine and pirfenidone for 48 weeks may lead to a worse prognosis of IPF ( Sakamoto et al, 2021 ). These clinical trials indicate that combination therapies for pulmonary fibrosis still need to be explored for a long time.…”

Section: Treatmentsmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

et al. 2022

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Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.

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“…We also analyzed the association between decline in FVC and treatment with the antifibrotic agents pirfenidone, nintedanib, and NAC, for each genotype. NAC has been used as inhaled form in Japan 20 , 21 . Although we found no significant interaction between rs3750920 genotype and antifibrotic treatment in our small sample, it is intriguing that FVC improved after inhaled NAC therapy in all 3 patients with the T allele (Fig.…”

Section: Discussionmentioning

confidence: 99%

Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese

Isshiki

Koyama

Homma

et al. 2021

Sci Rep

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TOLLIP polymorphism has been implicated in the development and prognosis of idiopathic pulmonary fibrosis (IPF), mainly in whites. However, ethnic differences in the characteristics of other interstitial pneumonia (non-IPF) subtypes are unclear. We evaluated the association between the rs3750920 genotype and the clinical characteristics of Japanese patients with fibrosing interstitial lung diseases (ILD). We genotyped 102 patients with fibrosing ILD (75 IPF and 27 non-IPF patients) and analyzed the interaction between the rs3750920 genotype distribution and their clinical characteristics. The overall frequencies of the C/C, C/T, and T/T genotypes were 69%, 25%, and 6%, respectively. The proportion of minor T allele carriers was larger in IPF patients than in non-IPF patients (37% vs. 15%, P = 0.031). In addition, survival at 3 years was significantly better for carriers than for non-carriers of the T allele. There was no significant association between genotype distribution and change in pulmonary function after introduction of antifibrotic agents. The frequency of the minor T allele of rs3750920 was low in Japanese patients with fibrosing ILD, particularly in non-IPF patients. Carriers of the minor T allele had better survival than non-carriers. Presence of the T allele might thus be an indicator of better outcomes for fibrosing ILD.

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Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial

Cited by 32 publications

References 26 publications

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese

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