INCREASE OLE data reflect long-term benefit of inhaled treprostinil for PH-ILD

Findings from the open-label extension (OLE) phase of the INCREASE study boost the efficacy and safety of inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD).

In the initial reports, exercise capacity as measured by 6-minute walk distance (6MWD) at week 16, as well as forced vital capacity (FVC), improved with inhaled treprostinil. [N Engl J Med 2021;384:325-334; Lancet Respir Med 2021;9:1266-1274] “Based on [the initial findings of] INCREASE, the US FDA approved inhaled treprostinil as the first and only treatment for PH-ILD,” said the researchers.

To further evaluate the long-term effects of inhaled treprostinil in this setting, 240 participants who completed the randomized phase and received at least one dose of the active study drug were enrolled in the OLE (n=119 and 121 of those previously assigned to inhaled treprostinil and placebo, respectively; median age 67 years, 52 percent male). To preserve prior blinding, all patients in the OLE were initiated on inhaled treprostinil at three breaths per session (bps) QID and titrated by an additional one breath QID every 3 days to a maximum dose of 15 bps QID as tolerated. [ATS 2022, abstract A5671]

The 6MWD improvements in the active arm of the parent study were maintained through 52 weeks with little decline. “[These indicate] that inhaled treprostinil has a durable, long-lasting response,” said the researchers.

Among placebo recipients who transitioned to inhaled treprostinil, a slower rate of decline was observed, implying minimal further deterioration of 6MWD.

“The differential response in 6MWD between the former placebo and active groups suggests a benefit to early initiation of therapy with inhaled treprostinil,” they explained.

FVC results also demonstrated long-term sustained improvement in lung function, both in patients initially assigned to inhaled treprostinil and among placebo recipients who switched to the active drug.

“The FVC improvements were encouraging,” the researchers noted. “The increase in FVC in the former placebo arm supports further investigation of the antifibrotic properties of inhaled treprostinil … Further research is also needed to understand why FVC improvements did not translate to improved 6MWD.”

At week 64, an increase in FVC was observed in a subgroup of patients with idiopathic pulmonary fibrosis who were previously receiving inhaled treprostinil and placebo (64 and 133 mL, respectively).

Adverse events (AEs) in the OLE aligned with the known tolerability profile of inhaled treprostinil. The most common AEs were dyspnoea (25 percent [active arm in parent study] and 27 percent [placebo arm in parent study]) and cough (18 percent and 36 percent, respectively). The incidence of cough though was lower in the active vs the placebo parent arm, as was the rate of headache (10 percent vs 27 percent), suggesting that longer exposure to the study drug may lead to improvement in these particular AEs, the researchers noted.

“[Taken together, the findings] provide evidence of the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent and supportive of the results observed in the 16-week randomized controlled trial,” they concluded.

Nonetheless, caution is warranted in interpreting data owing to the lack of a control arm, they stressed.

INCREASE OLE was discontinued upon US FDA approval of inhaled treprostinil for PH-ILD. All participants have been enrolled in the OLE for at least 60 weeks at the time of approval.