Efficacy, safety of nintedanib in Asian patients with IPF sustained in long term

Treatment with nintedanib slows disease progression of idiopathic pulmonary fibrosis (IPF) in Asian patients, and this beneficial effect persists over the long term, with acceptable safety and tolerability profile, suggest the results from a subgroup analysis of data from INPULSIS-ON, the open-label extension of the INPULSIS trials.

“Our analyses of data from the INPULSIS‐ON trial suggest that the safety and efficacy of nintedanib in Asian patients with IPF are maintained over the long term,” the researchers said. “These data from Asian patients are consistent with those observed in the overall trial population in INPULSIS‐ON.” [Lancet Respir Med 2019;7:60-68]

In this study, the long-term efficacy and safety of nintedanib was evaluated in patients of Asian ethnicity who were treated in INPULSI-ON. Analyses were descriptive.

Of the 215 Asian patients (mean age at baseline of INPULSIS-ON, 66.3 years; 80.5 percent male) treated, 121 continued nintedanib in the open-label extension study, and 94 who received placebo in INPULSIS trial initiated nintedanib. The mean forced vital capacity (FVC) of patients was 78.9 percent predicted. Median total exposure to the study drug in both studies stood at 42.2 months, with the maximum nintedanib exposure at 64.1 months. [Respirology 2020;25:410-416]

The annual rate of decline in FVC over 52 weeks was –124 mL/year in Asian patients treated with nintedanib and –218 mL/year in those who received placebo in INPULSIS. In the open-label extension, the annual rate of decline in FVC over 192 weeks was –127 mL/year.

Event rates of diarrhoea in Asian patients were 58.8 and 82.5 events per 100 patient exposure-years in those who continued and those who initiated nintedanib in INPULSIS-ON, respectively.

“The safety and tolerability profile of nintedanib observed in Asian patients participating in the INPULSIS and INPULSIS‐ON trials were consistent with that observed in the overall trial populations, with diarrhoea being the most commonly reported adverse event,” the researchers said. [N Engl J Med 2014;370:2071-2082; Lancet Respir Med 2019;7:60-68]

A real-world study of Korean patients who were treated with nintedanib also reported a similar safety and tolerability profile. [Respir Res 2018;19:203]

Previous studies suggested that the course and prognosis of IPF might differ between Asian and white patients. [Am J Respir Crit Care Med 2014;190:773-779; Respir Med 2006;100:451-457; Am J Respir Crit Care Med 2013;187:A4345; Respir Investig 2018;56:375-383]

However, the findings of the present study showed consistent annual rate of FVC decline in placebo-treated patients, as well as effect of nintedanib on FVC decline, between Asians and whites, and between Japanese patients and the overall population. [Am J Respir Crit Care Med 2016;193:178-185; Respirology 2016;21:1425-1430; Respirology 2017;22:750-757]

“It is unclear whether the small differences observed in the rates of acute exacerbations between Asian and White patients reflect differences between races or simply different methodologies used to recognize acute exacerbations in different countries,” the researchers said.

“Caution must be exercised in the interpretation of these data, given the small number of events observed and the challenges in classifying events as acute exacerbations of IPF,” they added.