4. Discussion
Pirfenidone and nintedanib have undergone rigorous clinical trials to
establish their efficacy and safety, emerging as major therapeutic
agents for IPF patients.[18] However, the related post-marketing
surveillance studies and pharmacovigilance analysis, which can provide
valuable insights into the long-term safety profiles of drugs, are
limited. In this study, we analyzed and compared the AEs and ADRs
induced by these drugs based on the FAERS and VigiAccess databases in
the real-world practice, thereby guiding clinicians in their use for the
management of IPF patients.
In our analysis, we found that male patients or patients over the age of
65 accounts for a large part of AE reports in the two databases, which
is consistent with previous study indicating that older age and male sex
are risk factors associated with IPF.[19] This epidemic character
might be explained by that male individuals tend to be smoker and its
occupational exposures. Hence, it is worth noting that the need for
heightened vigilance when administering pirfenidone or nintedanib,
especially in elderly and male individuals who may be more susceptible
to AEs.
ADRs manifest during routine clinical practice, contributing to
approximately 5% of hospitalization, affecting 10-20% of hospitalized
individuals.[20] It has been reported that pirfenidone and
nintedanib are both associated with several ADRs, with pirfenidone
primarily linked to gastrointestinal disorders, skin rashes or
photosensitivity, and nintedanib primarily linked to gastrointestinal
disorders, bleeding, cardiovascular events or myocardial
infarction[21, 22]. In this study, we aimed to find new and
unexcepted ADRs, so as to remind clinicians to beforehand detect
potential ADRs and timely make correct choice in decision-making
process. For pirfenidone in the FAERS database, the top five signals at
PT level are idiopathic pulmonary fibrosis, lung diffusion test
decreased, forced vital capacity decreased, forced vital capacity
abnormal, and sunburn. These signals notice us that although pirfenidone
can delay the decline in lung function in patients with IPF, it is still
unable to completely halt the progression of the disease, highlighting
the importance of regularly monitor various relevant indicators. And if
the respiratory symptoms are time-dependently worse with the use of
pirfenidone, temporary dosage reductions or discontinuations may be
required.[23] Moreover, wearing sunscreen and protective clothing
daily to avoid exposure to sunlight and sunlamps should be recommended.
For nintedanib, the top five are idiopathic pulmonary fibrosis, oxygen
saturation increased, cough decreased, oxygen consumption, lung
transplant, which also indicates that professional caregivers should
prevent and control the advent of these ARDs. In the VigiAccess
database, gastrointestinal disorders, including nausea, vomiting and
diarrhoea, accounts for majority ADRs of reports. It is imperative to
provide supportive care including antiemetic or antidiarrheal therapy at
first signs. Additionally, attention should be paid to signals that were
not mentioned in these drugs labels. Hemiplegic migraine occurred in the
use of pirfenidone, and asthenia, constipation, as well as flatulence
occurred in the use of nintedanib. This may indicate the need for
greater consideration to potential risks related to these ADRs during
the administration of pirfenidone and nintedanib.