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

Abstract

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.

Keywords

• Idiopathic pulmonary fibrosis
• Pirfenidone
• Acetylcysteine
• Meta-analysis
• Systematic review