No treatment benefit with pirfenidone plus sildenafil for IPF, pulmonary hypertension

Combination therapy with pirfenidone plus sildenafil did not provide treatment benefit in patients with advanced idiopathic pulmonary fibrosis and risk for pulmonary hypertension compared with pirfenidone plus placebo.

”There are no approved therapies for group 3 pulmonary hypertension and there is little evidence of antifibrotic drug use in patients with advanced IPF; therefore, the results of this study are important for patients with advanced IPF at risk of group 3 pulmonary hypertension and the clinicians involved in their treatment,” Jürgen Behr, MD, professor of pulmonary medicine in the department of internal medicine at the University of Munich Ludwig-Maximilians and director of the department of medicine at the University Hospital, Munich, and colleagues wrote in The Lancet Respiratory Medicine.

The researchers conducted a multicenter, international, double-blind, randomized, placebo-controlled phase 2 study that enrolled patients with advanced IPF and risk for pulmonary hypertension from January 2017 to August 2018. The researchers randomly assigned patients to 20 mg oral sildenafil (n = 88) three times a day or placebo (n = 89) in addition to 801 mg oral pirfenidone three times a day.

The primary endpoint was disease progression, defined as a relevant decline in 6-minute walking distance, respiratory-related hospital admission or all-cause mortality after 52 weeks. Researchers assessed safety in all patients receiving at least one dose of sildenafil treatment.

At 52 weeks, the proportion of patients with disease progression was 73% in the sildenafil-pirfenidone group vs. 70% in the placebo-pirfenidone group (between-group difference, 3.06%; 95% CI,–11.3 to 17.97; P = .65).

Fifty-four (61%) patients in the sildenafil-pirfenidone group and 55 (62%) patients in the placebo-pirfenidone group had serious treatment-related adverse events. Researchers observed adverse events leading to mortality in 22 (25%) patients in the sildenafil group and 26 (29%) patients in the placebo group. No new safety signals were found with either treatment group.

“The results of this study suggest that sildenafil should not be used in this group of patients; however, further research is required to establish if specific subgroups of patients might benefit from sildenafil,” the researchers wrote.