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.