Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis

Abstract

Background: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. Methods: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. Results: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. Conclusion: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.

Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a theoretical perspective

“…As a hypothesis, we suggest the combination of NAC and pirfenidone to be a potent and effective in the treatment of patients with COVID-19. Studies by Shi et al have revealed that the combination of these two drugs in patients with IPF did not affect the safety or efficacy when compared with single therapy of pirfenidone [ 132 ]. However, further investigation is needed in patients with COVID-19.…”

Pharmakotherapie der idiopathischen Lungenfibrose (ein Update) und anderer progredienter pulmonaler Fibrosen

“…Eine Metaanalyse aus dem Jahr 2019[85] beschreibt zwar einen positiven Effekt von N-Acetylcystein auf die FVC, einschränkend muss aber konstatiert werden, dass überwiegend nicht ausreichend gepowerte Studien mit geringen Fallzahlen sowie Studien, die eine Kombination von N-Acetylcystein mit Kortikosteroiden untersuchten, analysiert wurden. Die Kombination von N-Acetylcystein mit Pirfenidon als einem der aktuell für die IPF-Therapie empfohlenen Medikamente zeigt keinen Zusatznutzen hinsichtlich Lebensqualität oder einer Progressionsverlangsamung[86,87]. Die inhalative Gabe von N-Acetylcystein zusätzlich zu Pirfenidon scheint sogar einen schädlichen Effekt zu haben[88].…”

Efficacy of N-acetylcysteine plus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

“…The conclusions reached by these articles are inconsistent. Shi H et al [ 38 ] systematically reviewed these 5 articles and did not find that pirfenidone plus NAC had better benefits in the treatment of IPF. Nevertheless, a phase 3 RCT conducted by Sakamoto et al [ 18 ] in Japan found that NAC plus pirfenidone did not differ from pirfenidone monotherapy in terms of Δ%DLco, Δ6MWD, and progression-free survival in IPF treatment, and ΔFVC decreased more significantly.…”