New Treatments for the Deadly Idiopathic Pulmonary Fibrosis

FDA Just Approved Esbriet and Ofev for Idiopathic Pulmonary Fibrosis.

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In October 2014, the FDA approved two new drugs, pirfenidone (Esbriet) and nintedanib (Ofev), for treatment of idiopathic pulmonary fibrosis.  Idiopathic pulmonary fibrosis is a terrible disease that kills most people diagnosed with it in a few short years.  Before the discovery of pirfenidone and nintedanib, there were no specific drug treatment options for people with this deadly disease.

What Is idiopathic Pulmonary Fibrosis?

Idiopathic pulmonary fibrosis is a chronic or long-term disease which destroys the small spaces within the lungs (interstitia).

  Although limited data exists on the exact prevalence of the disease, the American Lung Association estimates that it hits about 140,000 Americans.  While perusing the literature, I saw much lower estimates when the disease is defined more restrictively (please excuse the pun), with it affecting anywhere from 14 and 28 people per 100,000. People with the disease are typically aged 50 years and older, and the disease affects more men than women.    

Nobody knows what causes idiopathic pulmonary fibrosis (which is why it’s called an idiopathic disorder).  What we do know is that this deadly disease increases recoil in the lungs—the lungs are an elastic organ—making it harder to breathe.  Of note, idiopathic pulmonary fibrosis is a restrictive lung disease that decreases lung volumes.  Once diagnosed, the median age of survival for people with the disease is a mere 4 years.

Idiopathic pulmonary fibrosis causes inflammation and fibrotic changes (scarring) in lung tissue (parenchyma) which is mechanically linked to pulmonary capillaries in the alveoli.

  The pulmonary capillaries in alveoli are thus destroyed; pulmonary capillaries are involved in oxygen exchange and introduce oxygen-rich blood into the body.  In other words, in people with idiopathic pulmonary fibrosis, scarring in lung tissue mucks up the ability for pulmonary capillaries to filter oxygen from the air that we breathe.

Idiopathic pulmonary fibrosis makes it hard to breath after exertion.  It also causes cough and a change in lung sounds on examination.  Many symptoms of the disease are systemic or body wide, too, and include fatigue, weight loss and clubbing of the fingers and toes.  High-resolution CT scans (imagine über-detailed x-rays) show a patchy or pied and “honeycomb” appearance where fibrotic changes have occurred.  Surgical biopsy provides a definitive diagnosis of the disease.  As pulmonary fibrosis progresses, it leads to a host of comorbid or concomitant conditions including respiratory failure, heart failure and pulmonary hypertension.

Although we are unsure what exactly causes idiopathic pulmonary fibrosis, we do know that there are some probable risk factors for the disease:

  • cigarette smoking
  • viral lung infections
  • inhalation of gas, fumes, dust and other small particles
  • GERD (gastroesophageal reflux disease AKA chronic heartburn)
  • genetics

Idiopathic pulmonary fibrosis is notorious for its lack of good and effective treatment.

  Although some people remain stable for a relatively long time after diagnosis, most decompensate or worsen even with treatment. Current treatment is aimed at symptoms of disease or attempts to limit further inflammation and scarring.  Prednisone, a steroid, is often used to help curb inflammation.  Many people with idiopathic pulmonary fibrosis also receive supplemental oxygen and pulmonary rehabilitation.  Ultimately, the only treatment option for people with idiopathic pulmonary fibrosis is lung transplant.

What Are Pirfenidone (Esbriet) and Nintedanib (Ofev)?

In clinical trials, pirfenidone (Esbriet) and nintedanib (Ofev) have been shown to mitigate fibrosis or scarring, and therefore slow progression of the disease.

Pirfenidone has multiple possible mechanisms of action and is an oral medication.  In Phase 3 clinical trials, nearly half the participants with mild to moderate idiopathic pulmonary fibrosis receiving pirfenidone saw a reduced decline in forced vital capacity.  This measure indicates delayed progression of the disease.  Participants experienced other positive benefits including improvements in 6-minute walking distance and decreases in mortality (number of deaths) during the 52-week study period.  Possible adverse effects of treatment were manageable and limited to photosensitivity, stomach cramps, nausea and vomiting.

Nintenanib is tyrosine-kinase inhibitor and like pirfenidone is an oral medication. Among other biologic processes, tyrosine kinase is involved in scarring and fibrotic change.  In Phase 3 clinical trials, like pirfenidone, nintenanib also slowed the progression of idiopathic pulmonary fibrosis as measured by a reduction in the rate of decline of forced vital capacity.  Potential adverse effects include diarrhea, nausea, vomiting, headache, increased blood pressure, and increased liver enzymes (an indicator of liver dysfunction).  Finally, Ofev is a teratogen that shouldn’t be taken during pregnancy for fear of fetal deformity or death.

What Do Pirfenidone (Esbriet) and Nintedanib (Ofev) Mean to You?

If you or someone you know has idiopathic pulmonary fibrosis, the approval of pirfenidone (Esbriet) and nintedanib (Ofev) Is a real medical breakthrough that should be welcomed as good news.  However, some issues need to be clarified before these drugs truly find their place in clinical medicine.  First, it’s unclear whether pirfenidone and nintendanib should be used separately or simultaneously when treating idiopathic pulmonary fibrosis.  If used together, we’re unsure which drug should be used first.  If used separately, we’re unsure whether the medications will display a synergistic or augmented effect.  Second, we’re unsure whether some people are particularly responsive (“responders”) to either or both of these medications.  Third, we don’t know if the drugs will continue to mitigate progression of idiopathic pulmonary fibrosis past the nearly yearlong test period.

On a final note, if you or a loved one has idiopathic pulmonary fibrosis, consider learning more about support groups for the disease at the American Lung Association or National Heart, Lung, and Blood Institute.

Selected Sources

“Recent Evidence for Pharmacolgical Treatment of Idiopathic Pulmonary Fibrosis” by JR Covvey and colleagues published in the Annals of Pharmacotherapy in 2014.  Accessed from PubMed on 11/4/2014. 

Naureckas ET, Solway J. Chapter 252. Disturbances of Respiratory Function. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. Accessed November 04, 2014.

Kemp WL, Burns DK, Brown TG. Chapter 13. Pulmonary Pathology. In: Kemp WL, Burns DK, Brown TG. eds. Pathology: The Big Picture. New York, NY: McGraw-Hill; 2008 Accessed November 04, 2014.

King TE, Jr.. Chapter 261. Interstitial Lung Diseases. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. Accessed November 04, 2014.

“Hot of the breath: a big step forward in for idiopathic pulmonary fibrosis” by  CJ Ryerson and HR Collard from BMJ published in September 2014.  Accessed from PubMed on 11/4/2014.

 

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