Kate Johnson

October 27, 2016

LOS ANGELES — Patients with idiopathic pulmonary fibrosis appear to benefit from antifibrotic therapy, irrespective of disease severity, according to four post hoc exploratory analyses.

"These drugs seem to have an effect across the board," said investigator John Belperio, MD, from the University of California, Los Angeles, who presented one of the analyses here at CHEST 2016.

The studies looked at pirfenidone (Esbriet, Genentech) and nintedanib (Ofev, Boehringer Ingelheim) and used data from the trials that led to the approval of both drugs.

The pirfenidone data come from RECAP, a long-term extension of the phase 3 CAPACITY trials.

In the first analysis, the 187 patients with severe idiopathic pulmonary fibrosis had a forced vital capacity (FVC) below 50% or a diffusing capacity of the lungs for carbon monoxide (DLCO) below 35%. This group was matched with 409 patients with less severe disease — an FVC of at least 50% and a DLCO of at least 35%.

All participants received open-label pirfenidone 2403 mg/day for 180 weeks.

The decline in FVC was similar in patients with severe and less severe disease (1.03% vs 1.11%). Results from a statistical prediction of the annual rate of decline in FVC were also similar in the two groups but were much higher, at around 3.5%.

Adverse events, such as nausea, diarrhea, and rash, were similar in the two groups, but discontinuation was more common in patients with severe disease than in those with less severe disease (approximately 70% vs 45%).

"This likely relates to progression of disease, as opposed to tolerability issues," said Paul Noble, MD, assistant clinical professor at Cedars–Sinai in Los Angeles, who presented the RECAP results.

In the second analysis of RECAP data, baseline FVC was stratified in 10% increments for 584 patients. The pattern of slow disease progression over the 180-week study period was similar in patients with severe and less severe disease, regardless of baseline FVC.

"Some physicians are hesitant to prescribe treatment in patients who are 'too good' or 'too bad' based on FVC, but these results show that patients with lower FVC may benefit from treatment," Dr Noble pointed out.

Similar Results From Nintedanib Analyses

An analysis of pooled data from two phase 3 INPULSIS studies looked at patients with idiopathic pulmonary fibrosis who were only marginally likely to benefit from the antifibrotic therapy.

For 52 weeks, 638 patients received nintedanib 150 mg twice daily and 423 received placebo.

Patients were stratified according to a composite physiologic index (CPI). The CT-based measurement of disease severity captures the functional impact of interstitial lung disease but excludes the impact of emphysema.

The reduction in disease progression — measured as decline in FVC of at least 5%, at least 10%, or death — was similar in nintedanib and placebo recipients whether baseline CPI was 45 or less or above 45.

There were "some tendencies for more frequent adverse events in those with CPI levels above the 45 threshold," said Athol Wells, MD, from Royal Brompton and Harefield NHS Trust and National Heart and Lung Institute, Imperial College London, in the United Kingdom, who presented the results.

However, "CPI thresholds show parallel findings to FVC thresholds, indicating that this observation is not an artefact of a single method of measuring severity," Dr Wells pointed out.

The same outcomes were used in the second nintedanib analysis, but patients were stratified by baseline GAP stage (gender, age, and predicted FVC and predicted DLCO).

Response to nintedanib was similar in the 536 patients with stage 1 IFP and the 560 patients with stage 2/3 disease, Dr Belperio reported.

"These results suggest that nintedanib reduces the risk of disease progression in patients with IPF, irrespective of severity of disease at baseline," he concluded.

However, post hoc findings can limit their application in clinical practice.

"These data are not from a randomized controlled trial," said session comoderator Prarthna Chandar, MD, from the Maimonides Medical Center in Brooklyn, New York. The findings are just "extrapolated from the data they already had," she told Medscape Medical News.

And her comoderator said she agrees. These are hypothesis-generating data, "as opposed to a call for change in practice," said Lioudmila Karnatovskaia, MD, from Mayo Clinic Rochester in Minnesota.

"It's hard to draw definitive conclusions and difficult to say, without a control group, whether these findings actually translate into clinical practice," she told Medscape Medical News.

Dr Belperio has financial relationships with Boehringer Ingelheim and is on the steering committee for the IPF-PRO registry. Dr Noble has financial ties to Boehringer Ingelheim, GlaxoSmithKline, Moerae Matrix, Pliant Therapeutics, and Roche/Genentech and has received research funding from the National Institutes of Health. Dr Wells has received lecturing and consultancy fees from Boehringer Ingelheim, Roche, InterMune, Actelion, and Bayer and editorial support from Boehringer Ingelheim.

CHEST 2016: American College of Chest Physicians Annual Meeting. Presented October 24, 2016.

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