Low-dose pirfenidone may be noninferior to standard dosing in patients with idiopathic pulmonary fibrosis

1. For patients with idiopathic pulmonary fibrosis (IPF), there was no difference in pulmonary function and efficacy between patients on low-dose pirfenidone compared to standard dose.

2. Patients on low-dose pirfenidone were more likely to be older than those on standard dose, and were also more likely to report experiencing gastrointestinal and skin side effects.

Evidence Rating Level: 2 (Good)

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a median survival of 3-5 years. While the antifibrotic drug pirfenidone is known to decrease decline of lung function in IPF patients, it is also associated with adverse gastrointestinal and skin-related events. Although some studies suggest low-dose pirfenidone is non-inferior to standard dosing, the burden of adverse side effects in low-dose pirfenidone is not well-known. Therefore, this single-centre study based in South Korea aimed to elucidate the factors associated with pirfenidone dose reduction. The study population consisted of IPF patients treated with pirfenidone, with 1 or more follow-up visits that assessed for adverse side effects. In this study, a standard dose was considered 1800 mg/day, whereas low-dose was less than 1800 mg/day. In total, there were 156 patients included, with a mean age of 69.7 years, and a median (IQR) follow-up of 243 (84-385) days. The study found that those taking low-dose pirfenidone were more likely older (71.0 years vs 67.4 years, p = 0.016), less likely to be ever-smokers (80.8% vs 96.4%, p = 0.008), and more likely to have a lower BMI (24.1 kg/m² vs 25.7 kg/m², p = 0.027). There were no differences in pulmonary fit test results, exercise capacity, or rates of pulmonary hypertension between the standard and low-dose groups, though more patients on standard dosing had emphysema (p = 0.048). After adjusting for sex, BMI, smoking status, and emphysema, older age was associated with reduction of pirfenidone dose (OR 1.066, p = 0.016). In addition, there were higher rates of some adverse events reported in the low-dose compared to the standard dose group, including anorexia (20.5% vs 3.5%, p = 0.004), urticaria (24.7% vs 10.5%, p = 0.039), and generalized weakness (9.6% vs 0.0%, p = 0.018). More broadly, the low-dose group experienced higher rates of gastrointestinal side effects (p < 0.01) and skin side effects (p = 0.020) than the standard group. Overall, this study demonstrated that older patients were more likely to be on low-dose pirfenidone, and that individuals in the low-dose group were more likely to experience side effects, though there were no differences in pulmonary function and efficacy of pirfenidone between the groups.

Image: PD

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