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There was no observed difference in proportion of disease progression between sildenafil combined with pirfenidone and placebo treatment groups.
New research suggests the combination of sildenafil (Viagra) and pirfenidone (Esbriet)—as compared with pirfenidone alone—does not provide greater treatment benefits in patients with advanced idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension.
Furthermore, the findings showed that the safety profile was similar for both the combination therapy and the standalone pirfenidone treatment.
Currently, there are no approved therapies for pulmonary hypertension in the context of severe pulmonary disease. The study underscores a necessity to develop new treatments for such patients who represent a group with a high medical need.
A team, led by Jürgen Behr, MD, Department of Internal Medicine, Ludwig Maximilian University of Munich, assessed the efficacy and safety of sildenafil plus pirfenidone in patients with advanced IPF who were also at risk of group 3 pulmonary hypertension.
The double-blind, randomized, placebo-controlled, phase 2b study was conducted at 56 university clinics, research hospitals, and tertiary across several countries. Investigators enrolled eligible patients (n = 247) aged 40-80 years.
Patients were then randomly assigned 1:1 to receive either oral sildenafil tablets (20 mg, 3 times daily) or placebo in combination with pirfenidone capsules (801 mg, 3 times daily).
The primary endpoint was disease progression, which the team defined as either a decline in distance for a six-minute walk, respiratory-related hospital admission, or all-cause mortality, after 52 weeks.
The efficacy date was assessed in the intention-to-treat population, and safety was assessed in all those who received a minimum of 1 dose of the investigative drug.
Investigators noted that the 11-month safety follow-up period is currently ongoing.
They found no difference in proportion of patients with disease progression between treatment groups. For those receiving sildenafil, 64 (73%) of 88 patients experienced disease progression—versus 62 (70%) of 89 patients in the placebo group.
The between-group difference was 3.06% (95% CI, -11.30 to 17.97; P = 0.65).
Additionally, Behr and team reported serious treatment-emergent adverse events in 54 sildenafil-treated patients and in 55 placebo-treated patients.
Treatment-emergent adverse events that led to mortality occurred in 22 patients in the sildanfil group and 26 patients in the placebo group.
In response to the seeming lack of treatment benefit from sildenafil, the team offered guidance for next steps in the assessment of sildenafil efficacy.
“Although the absence of a beneficial treatment effect suggests that sildenafil is not an appropriate treatment in the overall population, further research is required to establish if specific subgroups of patients with IPF might benefit from sildenafil,” Behr wrote.
The study, “Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial,” was published online in The Lancet Respiratory Medicine.