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Effects of IPF combination therapy similar for patients with, without right heart dysfunction

Among patients with idiopathic pulmonary fibrosis, the effects of nintedanib plus sildenafil, as compared with nintedanib alone, on quality of life and FVC did not differ significantly between patients with and those without evidence of right heart dysfunction, according to subgroup analyses of the INSTAGE trial.

“Exploratory analyses suggested that treatment with nintedanib plus sildenafil versus nintedanib alone was associated with a reduction in FVC decline and stabilization in brain natriuretic peptide (BNP), a marker of right ventricular strain,” the researchers wrote. “In this study, we investigated whether the presence of echocardiographic signs of [right heart dysfunction] at baseline influenced the effects of nintedanib plus sildenafil versus nintedanib alone in the INSTAGE trial.”

Of the 273 patients with IPF who were randomly assigned nintedanib (Ofev, Boehringer Ingelheim) plus sildenafil or nintedanib alone, 117 had echocardiographic evidence of right heart dysfunction at baseline and 156 did not.

Results showed no significant differences in the effect of nintedanib plus sildenafil vs. nintedanib alone on St. George’s Respiratory Questionnaire (SGRQ) score between patients with and those without signs of right heart dysfunction at 12 weeks (P = .74) and at 24 weeks (P = .9). The researchers noted the effect of nintedanib plus sildenafil vs. nintedanib alone on SGRQ total score was generally consistent among patients with right ventricular systolic dysfunction, right ventricular hypertrophy, right ventricular dilatation, paradoxical septum motion or right atrium enlargement.

There were also no significant differences in the treatment effect of nintedanib plus sildenafil vs. nintedanib alone on University of California San Diego, Shortness of Breath Questionnaire (UCSD-SOBQ) score in patients with and those without signs of right heart dysfunction at 12 weeks (P = .63) and 24 weeks (P = .8).

Similarly, the effect of nintedanib plus sildenafil vs. nintedanib alone on FVC did not differ significantly between patients with and those without signs of right heart dysfunction at 12 weeks (P = .58) and 24 weeks (P = .55). When compared with nintedanib alone, the combination therapy had a numerically greater effect on reducing FVC decline, again with no difference between those with and those without signs of right heart dysfunction (P = .29).

The HR for time to absolute decline in FVC of 5% or greater predicted or death favored nintedanib plus sildenafil vs. nintedanib alone, with no differences between patients with and without signs of right heart dysfunction (P = .28). Additionally, the HR for time to relative decline in FVC of 10% or more predicted or death also favored combination therapy vs. nintedanib alone, again with no difference between those with and those without signs of right heart dysfunction (P = .9).

Regarding change in BNP, however, the treatment effect of nintedanib plus sildenafil vs. nintedanib alone was more pronounced in patients with (–119.9 ng/L) vs. without signs of right heart dysfunction (–3.6 ng/L; P < .01).

“In conclusion, subgroup analyses of data from the INSTAGE trial demonstrated that the effect of nintedanib plus sildenafil versus nintedanib alone on changes in SGRQ total score and FVC were not significantly different between patients with or without echocardiographic signs of [right heart dysfunction] at baseline,” the researchers wrote. – by Melissa Foster

Disclosure: The INSTAGE trial was funded by Boehringer Ingelheim.