It kills as many people each year as breast cancer, but you may have never heard of it. Idiopathic pulmonary fibrosis, or IPF, is a deadly lung disease and until now there were no effective treatments. Now not one, but two new drugs are changing the game for people with the disease.
Robert Krabill can't go far before the symptoms of his disease start to show.
"It's when I get up and start walking around or going someplace or doing something, then the breathing takes its toll," Robert Krabill told Ivanhoe.
Robert has idiopathic pulmonary fibrosis or IPF for short. It's a disease that causes scar tissue to form on his lungs.
"Patients might experience shortness of breath, coughing, fatigue, inability to do the things they usually want to do," explained Daniel Culver, D.O., Pulmonologist and Staff Physician at Cleveland Clinic.
Those with IPF are typically given three to five years to live. Until now, there were no treatments to slow it down.
"If you compare IPF to many cancers, the prognosis for IPF is far worse," said Dr. Culver.
But two new FDA approved drugs are offering patients hope for the first time. In clinical trials, nintedanib and pirfenidone slowed down lung scarring and reduced breathing difficulties by about half. They are the first medicines approved to treat the disease.
Dr. Culver explained, "Having two medications where we had zero for so many years and where we gave people a death sentence for so many years when we made the diagnosis is a huge step forward."
Robert will start on the medication in the next couple of weeks. He hopes it will give him a little more time.
"See what happens and maybe be here a little longer," Krabill said.
These two drugs were approved by the FDA in October, 2014. IPF is the leading cause of lung transplants in the U.S. Experts aren't exactly sure what causes it but people who have experienced inhalation exposures to smoking or dust are more at risk.
BACKGROUND: Pulmonary fibrosis occurs when lung tissue becomes thick and stiff, or scarred over time. The thickening of the tissue blocks the flow of oxygen to the bloodstream resulting in a lack of oxygen to the brain and other organs. Idiopathic pulmonary fibrosis (IPF) is named when doctors are unable to find a cause. The disease usually affects middle-aged to older adults, and varies in rapidity from person to person. The most common cause of death for those diagnosed with IPF is respiratory failure, however other causes include: pulmonary hypertension, heart failure, pulmonary embolism, pneumonia and lung cancer.
(Source: http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/)
TREATMENT: Until recently, there was no cure for IPF; however treatments were given to help manage symptoms or slow the progress of the disease. Corticosteroids were given to help suppress the immune system; however it was not proved very effective as a long term treatment. Oxygen therapy, while it did not stop lung damage, made breathing and exercise easier, prevented or lessened complications from low blood oxygen levels, and reduced blood pressure in the right side of the heart. Pulmonary rehabilitation has been utilized to help patients with IPF live fuller lives by focusing on physical exercise (endurance), breathing techniques to improve lung efficiency, nutrition and counseling. As a drastic treatment, lung transplantations are performed when all other treatments are no longer beneficial.
(Source: http://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/basics/treatment/con-20029091)
FIRST- EVER TREATMENTS: As of October 2014, the FDA approved two drugs to treat IPF: pirfenidone (Esbriet), and nintedanib (Ofev). Pirfenidone's effectiveness was established in three clinical trials of 1,247 patients with IPF. The results of the trial showed a significant reduction in the amount of air which can be forcibly exhaled from the lungs after taking a deep breath, which is also referred to as forced vital capacity. Nintedanib was proven to have the same results as pirfenidone; however the three clinical trials were conducted using 1,231 patients with IPF. Daniel Culver, D.O., pulmonologist and staff physician at the Cleveland Clinic told Ivanhoe, "having two medications when we had zero for so many years…is a huge step forward." For more information on each of the drug's recommendations and side effects, visit the links below.
(Sources: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418991.htm, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418994.htm)
FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:
Andrea Pacetti
Cleveland Clinic Media Relations
(216) 444-8168
If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com
Daniel Culver, D.O., Pulmonologist and Staff Physician at Cleveland Clinic, discusses idiopathic pulmonary fibrosis and the two new treatments to cure it.
Interview conducted by Ivanhoe Broadcast News in October 2014.
Can we talk about what IPF is?
Dr. Culver: Idiopathic Pulmonary Fibrosis or IPF for short is a scarring disease of the lungs that tends to affect people in the later stages of life. Usually people who get IPF are over 50 years old. IPF tends to cause progressive loss of lung function and so patients might experience shortness of breath, coughing, fatigue, inability to do the things they usually want to do. And then of course the entire emotional component that comes with that hopelessness, sadness, depression, social isolation. It can be quite devastating and in fact it's a very significant diagnosis once it's made.
There's no known cause for IPF, correct?
Dr. Culver: IPF probably occurs because of a range of factors in the body. And also seems be exacerbated or there's a propensity towards it because of exposures. IPF tends to occur in people who have had some exposures such as inhalational things like smoking, some dust exposures, metal dust exposures, wood dust exposures. A number of things have been associated with development of IPF. None of those necessarily cause IPF but in a susceptible individual they certainly make it more likely to get it. When we think of IPF as a disease of scarring in the lungs, where the air sacs of the lungs, instead of healing normally after having some kind of an exposure or insult or an injury, heal by forming scar. Every time the lungs are injured there's a little but more scar and a little bit more scar until finally the lungs are very filled with scaring and it makes it very difficult to get a full breath in, difficult to get enough oxygen into the bloodstream, difficult to exert or do normal activities.
And the prognosis is generally pretty scary for these patients correct?
Dr. Culver: The prognosis of IPF is really quite poor and I think that's been an underestimated or neglected feature of IPF. IPF in general tends to cause death. Most of the estimates nowadays talk about maybe three to four years after the diagnosis of IPF about half of the people who have been diagnosed will be dead of their disease. If you compare IPF to many cancers the prognosis of IPF is far worse. And in fact it may be even worse to have IPF than cancer because up to now we haven't had any treatments. There's very little recognized about it so there's very little support and people feel quite isolated and end up having sometimes really bad deaths as a result.
Let's talk about the treatment actions. Up until now there really hasn't been much that we could offer patients that are diagnosed.
Dr. Culver: Yes, up until very recently we haven't been able to identify any compounds that can help with slowing down the scar formation or potentially even reversing it. For a number of years we tried to treat IPF as an inflammatory disorder with the theory being that there must be some inflammation which then led to the formation of scar tissue and that if we could just stop the inflammation that we would halt IPF. But in fact we discovered that some of the anti-inflammatory treatments can in fact be harmful rather than helpful or notice some gain for IPF patients. Now we have two medicines that have been approved by the FDA just in the last week. Those are pirfenidone and nintedanib. And those are medicines that more specifically target the process of fibrosis or scarring. And so to me they make a lot of biologic sense and certainly the trials that have been done bear that out. They seem to be helpful for people. Pirfenidone has been approved in other countries for several years it was first approved in Japan a few years ago. And then in the last three years or so it's been more widely used in Europe, Canada, South America, some places in Africa. So pirfenidone has been in use for a few years, nintedanib on the other hand was only just approved this week for the first time in any country.
How do they work?
Dr. Culver: We don't know exactly how either of the drugs work. Pirfenidone seems to have a number of activities that can inhibit pathways that are important in the formation of scar tissue and in the activation of one of the cells that really helps drive scaring called the fibroblast. Nintedanib blocks three receptors that are important in the development of scar tissues. I think we understand more about how nintedanib works but can I say that we understand all the biological pathways perfectly, no we cannot.
What does this mean for the field to finally have some type of option to offer patients?
Dr. Culver: Having two medications where we had zero for so many years and we gave people a death sentence for so many years while we made the diagnosis is a huge step forward. I think this is a big inflection point in the treatment of idiopathic pulmonary fibrosis. In terms of what the medications can do, both of them look like they slow down the progression of IPF; so where we might talk about the lung function deteriorating every six months or every year by a certain percentage we can say that with these medicines that, that deterioration is cut by about 50 percent. We also think that the mortality rate is probably cut by both of these drugs to some degree so therefore life expectancy would be longer in patients taking these drugs on average. We think the number of exacerbations is cut down by these medications most likely and there are some data suggesting that people who use these medicines compared to placebo are able to walk a little bit further and have a little bit more quality of life, a little fewer symptoms. I think there's another thing that we might underestimate when we think about cold hard numbers and that is the psychological impact to patients of knowing that there's something for them. That somebody has done something that is there to help them. That is like throwing a life preserver to someone who's drowning; it's a very important thing in their mind.
It gives them hope?
Dr. Culver: It gives them hope. Both of the drugs seem to slow the rate of decline in lung function over time, cut down the number of exacerbations, probably prolong life and also improve quality of life. If one thinks about the kind of symptoms that somebody with IPF has like shortness of breath, coughing and all of the psychological things that come along with having a devastating disease I don't think that we can say today that either nintedanib or pirfenidone necessarily would have a different impact on those symptoms. I think we'll need to get some more experience with using those before we know exactly what the nuance differences are between the two of them.
Now that we have these two drugs, are there more drugs that are kind of in the pipeline? What's the next step?
Dr. Culver: This is a very exciting time in drug discovery. This is a very exciting time in medication development for IPF because we have now taken a focus of looking at fibrosis or scarring instead of looking at inflammation there are a number of drugs in the pipeline that look very promising. We like the biology of a number of the compounds that are coming down the pike. I think a challenge will be now that there are two medications on the market that will be standard of care most likely we'll be proving that the new medications are better or that they add something to the two medications that are already here. There's a real challenge for clinical trial design and it's my ardent hope that we're able to still investigate those effectively and figure out whether or not any of them work. But yes I think the biology of IPF really is starting to become untangled in a way that gives us some real targets and some real hope for medications that may be even better than these two. I would envision that IPF very well may be managed similar to what we do with heart failure in the future where we may use a combination of several different medications in lower doses to attack multiple pathways or multiple parts of the problem. I think the idea of taking a complex disease like IPF and only inhibiting one pathway or one molecule probably is not going to get us where we ultimately need to be. It's probably is not going to get us where we ultimately need to be but I think this is a tremendous start.
Is there anything else you feel like it's important to cover?
Dr. Culver: Both nintedanib and pirfenidone are approved for IPF but not for other scarring lung diseases, they're also both quite expensive and have some toxicities. These are generally mild to moderate toxicities but I think it's important before anybody goes on pirfenidone or nintedanib that they be assessed and at least seen periodically by somebody with real expertise in interstitial lung diseases. The diagnosis of interstitial lung diseases can be tricky and I think these sorts of medicines require a little bit of circumspection.
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