Sildenafil (Viagra) does not improve quality of life for idiopathic pulmonary fibrosis patients treated with nintedanib (OFEV)

1. In patients with idiopathic pulmonary fibrosis (IPF) and a low diffusion capacity for carbon dioxide (DLCO), the addition of sildenafil to a treatment regimen of nintedanib did not improve quality of life scores after 12 weeks compared to treatment with nintedanib and a placebo.

2. Dyspnea symptoms did not improve with the use of sildenafil in addition to nintedanib.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: IPF clinically results in significant decreases in lung function and quality of life for affected patients. Sildenafil is a drug approved for use in pulmonary hypertension, though its efficacy in IPF patients with pulmonary atrial hypertension secondary to lung disease has not been shown. A prior study indicated sildenafil can improve IPF patient quality of life scores and reduce symptoms of dyspnea. In this INSTAGE trial, the efficacy of sildenafil in addition to approved IPF treatment with nintedanib is evaluated for the effect sildenafil has on patient quality of life scores. After 12 weeks of treatment with either nintedanib alone or nintedanib plus sildenafil, there was no significant difference in quality of life scores. Secondary end points including symptoms of dyspnea and episodes of acute exacerbations were also similar between the two study groups.

Strengths of this study included inclusion of patients with low DLCOs, rigorous evaluation of side effects, and numerous secondary endpoints evaluated. Limitations include the short duration of the trial and limited number of enrolled patients, both of which contributed to the possibility that this study was underpowered to detect clinical differences in the treatment groups.

Click to read the study, published today in NEJM

Relevant Reading: A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis

In-Depth [randomized controlled trial]: This international, double-blind, randomized controlled trial enrolled patients between 2016 and 2017. Patients were eligible if they were 40 years or older, had been diagnosed with IPF within the prior 6 years, and had a DLCO of 35% or less of the predicted value. Eligible patients were randomized to either a nintedanib group plus placebo (n=136) or a nintedanib plus sildenafil group (n=138). Patients were treated and followed in the study for 24 weeks. The primary end-point was the change from baseline in the SGRQ (St. George’s Respiratory Questionnaire) quality of life score at 12 weeks, which for the nintedanib-sildenafil group was -1.28 points and -0.77 points for the nintedanib-placebo group (P=0.72). Additionally, at 24 weeks there was no significant difference in SGRQ scores between treatment groups. When specifically evaluating dyspnea symptoms, there was also no significant difference between groups at either 12 or 24 weeks of treatment. Secondary end-points evaluating lung function, including measurements of change from baseline in forced vital capacity, oxygen capacity, and DLCO did not significantly differ between the treatment groups at either 12 or 24 weeks or treatment. Side effect profiles, occurrences of acute exacerbations, and all-cause mortality were all similar between the two groups.

Image: PD

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