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.