1. Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) characterized by the development of excessive fibrotic tissue in the lungs, leading to impaired respiratory function, and an increased risk of respiratory failure or complications causing mortality.[1] Despite extensive research efforts, the exact etiology of IPF remains elusive, and its prognosis remains poor, with a median survival time of only 2-3 years after diagnosis, not to mention the elderly over the age of 65 years.[2] Nonpharmacologic interventions play a crucial role in enhancing the overall well-being and quality of life for IPF patients, enabling them to lead healthier lives.[3] Moreover, among the limited treatment options currently, two antifibrotic drugs, nintedanib and pirfenidone, are recommended as first-line treatment for IPF, which have shown promise in slowing progression, preserving lung function, and improving patient outcomes.[4]
Pirfenidone exerts regulatory effects on fibrogenic growth factors, especially transforming growth factor (TGF)-β1, thereby mitigating the proliferation of fibroblasts, differentiation into myofibroblasts, as well as the synthesis and deposition of collagen, fibronectin, and other extracellular matrix (ECM) components.[5] It has been shown to reduce the decline in forced vital capacity (FVC) and improve progression-free survival in patients with IPF.[6] Pirfenidone was firstly approved for treatment of IPF in Japan, and has subsequently gained clinical recognition in America and Europe. Nintedanib, a triple angiokinase inhibitor, stands as another disease-modifying therapy approved and indicated for the treatment of IPF. It targets key pathways involved in fibrogenesis, including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) signaling.[7] Clinical trials such as INPULSIS trials have demonstrated that nintedanib reduces the annual decline in FVC and slows disease progression in IPF patients, leading to its first approval as a treatment option for IPF in the United States in 2014.[8]
Despite demonstrating favorable therapeutic effects, drugs can similarly bring the inevitable risk of causing unforeseen harm known as adverse events (AEs), affecting effects of drug, prognosis and outcome of patients.[9] In addition, adverse drug reactions (ADRs), defined as the unexpected and harmful response that occurs during drug administration, should also be taken seriously.[10] The administration of pirfenidone in clinic has been associated with gastrointestinal symptoms, skin rashes and the occurrence of significant liver function abnormalities, necessitating regular monitoring as recommended.[11] Moreover, ADRs related to pirfenidone demonstrate a dose-dependent relationship and can be ameliorated through adjustments in mode and dose of administration.[12] The reported common ADRs associated with nintedanib were diarrhea, bronchitis, nasopharyngitis and cough.[13] And the occurrence of these in hospitalized patients not only imposes financial burden on patients, but also prolongs their hospital stay, and in severe cases, poses a threat to their life. Therefore, it is crucial for clinicians to have a thorough understanding of these potential ADRs, as close monitoring and prompt management can help mitigate the impact of these ADRs.
While clinical trials play a crucial role in establishing the efficacy of novel medications and identifying common ADRs, they may not capture all real-world scenarios due to the potential for rare and severe events that may only emerge after widespread administration of the drug in clinical settings. Fortunately, the emergence of pharmacovigilance (PV) analysis compensates for this deficiency. PV analysis plays a crucial role in monitoring and evaluating the safety profile of pharmaceutical products. Data sources such as the FDA Adverse Event Reporting System (FAERS) and the World Health Organization’s VigiAccess database enable the collection, analysis, and assessment of ADRs and other medication-related safety issues on a population level.[14]
In the present study, we conducted a statistical analysis of the data gathered from the FAERS and VigiAccess databases to identify the AEs and ADRs signals associated with pirfenidone and nintedanib. In addition, we visually depicted the categories of AEs for both drugs and compared the the risk of ADRs between them, so as to provide valuable insights into the safety of clinical medication and support evidence-based decision-making in drug selection.