Combining Ofev (nintedanib, marketed by Boehringer Ingelheim) with sildenafil does not offer additional clinical benefits when compared to Ofev treatment alone regarding quality of life and lung function in patients with idiopathic pulmonary fibrosis (IPF) and a very poor lung function, a Phase 3 study demonstrates.
The study, “Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis,” was published in the The New England Journal of Medicine.
Data from a prior Phase 3 clinical trial (NCT00517933) suggested that 12-weeks of treatment with sildenafil (brand name Revatio, marketed by Pfizer), an oral medication approved for pulmonary arterial hypertension, was able to reduce some symptoms in patients with IPF and a severely reduced lung gas exchange capacity (less than 35% of the normal diffusing capacity of the lungs for carbon monoxide, called DLCO).
Although treatment with sildenafil did not improve exercise tolerance (measured by the six-minute walk test) compared to placebo, it did lead to small but significant improvements in blood oxygenation, DLCO, and quality of life in these patients.
Based on those results, researchers set out to test the hypothesis that combining sildenafil and Ofev, a medication approved for IPF, would lead to larger improvements in patients’ symptoms, compared to Ofev treatment alone, specifically in patients with poor lung gas diffusion function.
The team evaluated the safety and effectiveness of the combo treatment in a multicenter, double-blind, randomized Phase 3 trial (NCT02802345), which included 274 patients, ages 40 or older, with IPF and a DLCO of 35% or less of the predicted value. Patients were recruited from centers in 13 countries, including the U.S., Canada, Australia, and in Europe.
Patients were randomly assigned to receive either Ofev 150 mg twice daily plus sildenafil 20 mg three times daily, or Ofev 150 mg twice daily plus placebo three times daily for 24 weeks.
The primary endpoint of the trial was a change in health-related quality of life, assessed by the St. George’s Respiratory Questionnaire (SGRQ. A higher score indicates a better health-related quality of life. Secondary endpoints included measures of dyspnea (shortness of breath) and safety.
No significant differences were seen between the combo therapy or Ofev alone in terms of health-related quality of life at week 12 or week 24 after treatment.
Patient-reported dyspnea changes from baseline also did not significantly differ between treatment groups, nor did blood oxygen saturation or DLCO at weeks 12 and 24.
Forced vital capacity (FVC), however, which refers to the volume of air in liters the lungs can sustain, tended to decline more slowly in the Ofev plus sildenafil group than in the Ofev group. A total of 25.5% of patients receiving the Ofev plus sildenafil combo had a relative decline of at least 10% of the predicted FVC value or died, compared with 36.8% in the Ofev group.
Acute exacerbations (7.3% vs. 7.4%) or deaths from any cause (10.2% vs. 11.0%) were similar between both Ofev plus sildenafil and the Ofev-only groups, respectively.
Both treatment groups shared similar safety profiles, with no new safety signals observed as compared to those reported for the two medicines.
Diarrhea was the most frequent adverse event in both the combo treatment (57.7%) and Ofev alone (48.5%), and a similar proportion of serious events occurred in the two groups (27.0% vs. 32.4%, respectively).
In total, 13.9% of the patients in the Ofev plus sildenafil group and 16.9% of those in the Ofev group discontinued the trial due to adverse events.
“In conclusion, combination therapy with [Ofev] plus sildenafil did not provide a significant benefit as compared with nintedanib monotherapy in patients with IPF and severe impairment in gas exchange,” the researchers wrote.