Dr Hayley Barnes

Inhaled treprostinil shows some promise as a treatment for pulmonary hypertension associated with ILD, according to US research.

The study randomised 326 patients to treprostinil (0.6 mg per ml) or placebo delivered by a nebuliser four times daily for 16 weeks. Doses were escalated from three to a maximum tolerated dose of up to 12 breaths per treatment session.

The study, published in the NEJM, found the change from baseline in 6-minute walk distance at 16 weeks was significantly improved by 31.12 m in the treated group as a whole compared to controls.

The 6MWD increased by 21.08 m in the treprostinil-treated group and decreased by 10.04 m in the controls.

“Similar effects were observed across subgroups, including subgroups defined by disease cause and severity (as measured by baseline 6-minute walk distance), baseline haemodynamics, and dose group,” the study said.

In secondary and exploratory endpoints, the NT-proBNP level decreased 15% from baseline with inhaled treprostinil and increased 46% from baseline with placebo.

Clinical worsening occurred in fewer treated patients than controls (22.7% v 33.1%; p<0.001) however there was no significant difference between the groups in patient-reported quality of life.

The most commonly reported adverse events included cough, headache, dyspnea, dizziness and nausea of mild to moderate intensity. Serious adverse events occurred in 23.3% of the treprostinil-treated group and 25.8% of controls.

Significantly fewer patients in the treprostinil group had exacerbations of underlying lung disease (26.4% v 38.7%; p=0.02) and treprostinil was not associated with any worsening of lung function measures.

“The safety profile of inhaled treprostinil observed in this vulnerable patient population was similar to that reported in previous studies,” the researchers said.

An accompanying editorial in NEJM said “demonstrating a placebo-corrected improvement in exercise capacity with treprostinil is exciting.”

“Will it be important for patients? Prevention of deterioration is not to be ignored, even if it does not make a patient feel better,” NEJM deputy editor Adjunct Professor Darren Taichman wrote.

“Now we need additional, longer-term data to see whether patients will feel better or live longer and to identify which patients and at what costs.”

Melbourne respiratory physician Dr Hayley Barnes told the limbic that the improvement in 6MWD was clinically meaningful.

“In this group of people, either ILD or PH, the minimal clinically important difference is between 20 and 31 metres so it does meet what patients have previously reported in other studies to be worth it.”

“This is the first study that has come out and said there is some potential benefit in this PH-specific drug in this group of patients which I think is pretty exciting.”

Dr Barnes, from Alfred Health, said lung function typically deteriorates in these patients with drugs currently approved for other types of ILD or with placebo.

“In this study there were concerns the lung function might go down because of the side effects of the drug but it actually stayed the same in the treatment group. It suggests that maybe a bit more work needs to be done in this area to see whether there will be a slight improvement or even stability in lung function which we have never really seen before.”

“Certainly the FVC didn’t decrease [with treatment] and that was statistically significant and the DLCO was probably no real difference between the two groups.”

She said an inhaled treatment was more convenient than IV options.

“And the authors are also wondering whether this [the mode of administration] explains why this drug appears to do better than some of the other drugs that have been trialled in the past. They are wondering if because the drug goes straight into the lungs, rather than having to be absorbed, maybe this is why they are getting better results than in the past.”

Dr Barnes reiterated the editorial’s call for more research.

“It’s a short time, only 16 weeks, so more work is probably needed for a longer term study. But if the same results came out over the course of a year, this is pretty exciting for this group of patients who generally do worse than the general group of ILD patients.”

Disclosures: The study was funded by United Therapeutics whose product pipeline includes inhaled treprostinil. Dr Barnes reported no conflicts of interest relevant to the study.