New guidelines for idiopathic pulmonary fibrosis

The Lancet 25th July 2015

International experts in idiopathic pulmonary fibrosis (IPF) have issued new treatment guidelines to reflect the advances made recently in this terminal disease.

Survival for people with IPF—a chronic, progressive, fibrosing form of interstitial pneumonia—was historically around 50% at 3 years.
Treatment options have centred on best supportive care including oxygen and pulmonary rehabilitation. Pharmacological disease-modifying interventions have been disappointing.
Combination therapy with prednisone, azathioprine, and N-acetylcysteine showed promise, but the results of the PANTHER-IPF study showed an excess of deaths and serious adverse events without evidence of benefit. This result is reflected in the strong recommendation against this treatment in the 2015 guidelines.

There are several other important changes in these guidelines issued jointly by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Association.
Two new agents are given conditional recommendations (suggesting that they might be suitable for some patients): nintedanib, a tyrosine kinase inhibitor; and pirfenidone, an oral antifibrotic drug.
Pooled data on nintedanib show no significant effect on mortality or acute exacerbations of IPF, but a reduction in decline of forced vital capacity (FVC).
Available trial data for pirfenidone show both a reduction in mortality and a reduced rate of FVC decline.

The guidelines make strong or conditional recommendations for or against potential therapeutic agents, allowing physicians and patients to individualise treatment decisions.
Strong recommendations are made against warfarin; imatinib, a selective tyrosine kinase inhibitor; and ambrisentan, a selective endothelin receptor antagonist.
Conditional recommendations are made against sildenafil, a phosphodiesterase-5 inhibitor; and the dual endothelin receptor antagonists, macitentan and bosentan.

The new 2015 guidelines encapsulate the hope offered by new agents, but also draw attention to important gaps that remain in our knowledge of this devastating disease, and emphasise the importance of further high-quality clinical trials with clinically meaningful endpoints and long-term follow-up data.

G Mohan