Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

Abstract

Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience

“…Real-life studies directly comparing discontinuation of therapy between the two drugs are scarce, and most ended within 2 years after initiation. However, the discontinuation rate in our study was lower for both pirfenidone and nintedanib in comparison with the literature [ 14 , 17 , 18 , 20 , 21 ]. This may be, at least in part, because we had only one patient drop out for lack of efficacy, and we excluded from the count those patients who had died on therapy.…”

“…This may be, at least in part, because we had only one patient drop out for lack of efficacy, and we excluded from the count those patients who had died on therapy. The results of real-life studies are often conflicting: some are in favour of pirfenidone, and others in favour of nintedanib [ 21 , 22 , 23 ]. Variables that have been associated with an increased risk of treatment discontinuation are older age [ 17 , 18 , 23 ], female sex [ 23 ], FVC%pred < 60% [ 24 ], and use of supplemental oxygen [ 23 ].…”

Component analysis and anti-pulmonary fibrosis effects of Rosa sterilis juice

“…3,4 Progressing dyspnea and cough are the main clinical symptoms of lung fibrosis, and patients eventually die from respiratory failure. 5 However, current drugs can only slow the progression of the disease, 6 leaving pulmonary fibrosis still an incurable disease, and effective antifibrotic therapies are urgently required. Natural products have attracted increasing research attention in recent years.…”

State of the Art in Idiopathic Pulmonary Fibrosis

“…Moreover, they possess a marked side-effect profile, which may lead to the discontinuation of antifibrotic therapy. In this Special Issue, Takehara et al [ 26 ] retrospectively analyzed the discontinuation rates of pirfenidone and nintedanib in a cohort of 261 patients in Japan, 77 of which were excluded because either the antifibrotic agent was switched or the observation period was less than a year. Analysis of the remaining patient data showed that the discontinuation rate was around half within one year of treatment.…”

“…Discontinuation due to disease progression or hospital transfer was higher for pirfenidone than nintedanib. The authors associated the adverse effects of nintedanib with a lower body mass index (BMI) and recommended a reduced starting dose and closer attention paid to adverse events at the initiation of nintedanib treatment to improve tolerability, achieve longer treatment, and improve prognosis [ 26 ].…”