Is nintedanib safe, effective in patients with early-stage IPF?

Results of nintedanib use in patients with early-stage idiopathic pulmonary fibrosis (IPF) show a stable change in forced vital capacity (FVC) and a gradual decline in diffusing capacity of the lungs for carbon monoxide (DLCO) at week 52, according to an ongoing study presented at APSR 2023. In addition, treatment discontinuation is comparable to that in previous clinical trials.

In univariate analysis, nintedanib discontinuation was significantly associated with age (odds ratio [OR], 1.049, 95 percent confidence interval, 1.004‒1.110; p=0.04), GAP score (OR, 1.18, 95 percent CI, 1.037‒1.362; p=0.013), and forced expiratory volume (FEV1)/FVC ratio (OR, 1.070, 95 percent CI, 1.026‒1.120; p=0.003). [Sakamoto N, et al, APSR 2023]

Diarrhoea (n=17, 7.9 percent) was the leading cause of treatment discontinuation. This was followed by IPF progression (b=13, 6.0 percent), liver function test elevations (n=9, 4.2 percent), decreased appetite (n=7, 3.3 percent), nausea (n=4, 1.9 percent), and vomiting (n=3, 1.4 percent), among many other adverse events (AEs).

Antifibrotic therapies are known to lead to several AEs, such as gastrointestinal events. In the INPULSIS trials, diarrhoea was also the most common AE, occurring in 62.4 percent of patients treated with nintedanib compared with 18.4 percent of those who received placebo. [Respir Res 2015;16:116]

“Although most of the AEs of nintedanib are controllable, the risk–benefit balance of nintedanib treatment for patients in the early stage of IPF should be clarified in a real-world setting,” according to the investigators. [BMJ Open 2021;11:e047249]

Lead author Noriho Sakamoto from the Department of Respiratory Medicine at Nagasaki University Graduate School of Biomedical Sciences in Nagasaki, Japan, and his colleagues conducted this ongoing, prospective, multicentre observational cohort study “to clarify the efficacy, safety, and tolerability of nintedanib in patients with early-stage IPF.”

They enrolled a total of 215 patients with stage I/II IPF (mean age 71.8 years) at 35 sites in Kyushu and Okinawa, Japan. Majority of the participants were male (n=169, 78.6 percent).

Preliminary findings

“In [previous] clinical trials of IPF, nintedanib has been reported to have inhibitory effect on reduced lung function, incidence of acute exacerbation, worsened health-related quality of life, [and] all-cause and on-treatment mortality,” Sakamoto said. [N Engl J Med 2014;370:2083-2092; N Engl J Med 2014;370:2071-2082; Lancet Respir Med 2019;7:60-68]

“However, effectiveness and safety outside of clinical trials especially in early-stage IPF remain unclear,” he added.

One-year findings from the current study revealed a change in FVC from 90.0 percent 6‒15 months before treatment to 83.7 percent at week 52 and that in DLCO from 73.8 percent before treatment to 64.2 percent at week 52.

Of the patients, 10 (4.7 percent) had first acute exacerbation of IPF at 52 weeks. Ten deaths have occurred thus far, most of which were due to acute exacerbation (n=7), while the rest were caused by respiratory failure, malignant tumour, and pneumonia (n=1 each).

“To the best of our knowledge, this is the first prospective, multicentre observational cohort study to clarify the efficacy, safety, and tolerability of nintedanib in Japanese patients with early-stage IPF classified according to the Japanese IPF disease severity staging classification system,” the authors said.

“IPF is a fibrotic disease of unknown aetiology with a poor prognosis,” they noted.