THE CLINICAL COURSE OF PF IS HIGHLY VARIABLE and may be difficult to predict. As a result, strategies to treat PF are highly individualized, based upon the specific patient’s medical history and other conditions. While there is no cure or FDA-approved treatments for IPF in the United States, and there are limited treatment options in the EU, Canada, and Asia, there are a variety of therapeutic options to help patients manage their condition and maintain their quality of life and activities of daily living. Typical standards of care may include prescription therapies, supplemental oxygen, pulmonary rehabilitation, lung transplantation, and/or referral for clinical trial participation. Lung transplantation remains the most viable course of treatment to extend the lives of those with IPF; this option should be discussed with your physician.
For some patients, depending upon their specific type of PF, medications may stabilize their disease and there may be a benefit to continuing usage. Further, some of these medications may be prescribed to manage symptoms when a patient has an acute exacerbation or period of worsening. Medications may be used alone or in combination.
It is important to note that patients with IPF taking or prescribed “triple combination therapy” with corticosteroids, azathioprine, and N-acetylcysteine (NAC) should discuss the risks and benefits of this combination therapy with their health care provider.15
The international IPF guidelines note that some therapeutic agents may provide a possible benefit for some patients. As with any medication for any condition, patients should discuss specific treatment options directly with their physician to determine the best approach for their care.
The following medications may be prescribed for the treatment of PF:
PHARMACOLOGIC TREATMENT OPTIONS
Corticosteroids (prednisone): Prednisone is used for suppressing the immune system and inflammation. It mimics the action of cortisol that is produced by the adrenal glands. Depending on the dose, prolonged therapy can cause the adrenal glands to stop producing cortisol. For this reason, when prednisone is discontinued, it may be necessary to gradually lower or taper the dose to allow time for the adrenal glands to recover. Since prednisone suppresses the immune system, it can potentially increase the frequency and severity of infections. Prednisone has many side effects, so individuals receiving prolonged treatment or higher doses need to be carefully monitored.
Cyclophosphamide (Cytoxan®): Cytoxan® is an anticancer drug frequently given in conjunction with prednisone or that may be given alone. While it is usually taken daily by mouth, in some instances it may also be administered intravenously.
Azathioprine (Imuran®): Imuran® is used to suppress the immune system and is commonly used to treat autoimmune diseases such as RA. It is also used to help prevent the body from rejecting organs following transplantation. Although there have been some successful reports in a small number of individuals, the effectiveness of Imuran® to treat IPF has not been confirmed in a randomized clinical trial to date.
N-acetylcysteine (NAC): NAC is a naturally occurring antioxidant. It can be taken orally and theoretically could prevent some of the oxidative injury that precedes an increase in fibroproliferation. A small, non-randomized study demonstrated some improvement in lung function in patients with IPF. There are a number of ongoing studies investigating the efficacy of NAC in combination with other drugs to treat IPF.
Pirfenidone (Esbriet®, Pirfenex®, Pirespa®): Pirfenidone is an anti-fibrotic and anti-inflammatory drug approved to treat mild-to-moderate IPF in the EU, Canada, and Asia. In other countries, including the US, pirfenidone is still undergoing clinical trials to investigate the efficacy of pirfenidone to treat IPF in order to meet regulatory requirements.
Supplemental Oxygen Therapy: As fibrosis inhibits an adequate transfer of oxygen into the bloodstream, some patients may require supplemental oxygen. This helps to reduce breathlessness, enabling the patient to be more active. Some patients may need oxygen therapy all the time while others may only need it during sleep and exercise. By testing the saturation level of oxygen in a patient’s blood, a physician can determine if a patient requires supplemental oxygen.
If your doctor has prescribed supplemental oxygen, it is important to use it as prescribed. Many patients are fearful that they will become “addicted” to supplemental oxygen. It is important to recognize that supplemental oxygen is not addictive. The proper amount of oxygen in the bloodstream is necessary to maintain normal body functions. Low blood oxygen levels can lead to additional health problems.
It is important to note that medications utilized in the treatment of PF can vary by phenotype or cause of PF.
In addition to pharmacological treatments, patients with PF have non-drug options for treatment:
NON-PHARMACOLOGIC TREATMENT OPTIONS
Pulmonary Rehabilitation: Pulmonary rehabilitation includes conditioning; exercise training and breathing exercises; anxiety, stress, and depression management; nutritional counseling; education; and other components. The goal of pulmonary rehabilitation is to restore the patient’s ability to function without extreme breathlessness. It has become the standard of care for people with chronic lung disease, and recent studies have demonstrated improvements in both exercise capacity and health-related quality of life in patients with IPF.16 These programs offer a variety of services and can be inpatient, outpatient, or home/community based. The programs are multidisciplinary, meaning that the team includes nurses, respiratory therapists, physical therapists, social workers, dieticians, and others.
Lung Transplantation: IPF is now the leading indication for lung transplantation in many large transplant centers. Transplantation can improve both longevity and the quality of life in properly selected patients who have no other significant health problems. Previously, it was uncommon for individuals over the age of 65 to receive transplants. However, as surgical techniques and outcomes have improved more centers are performing transplants in individuals over age 65.
Until recently, early referrals were essential because of long pre-transplant wait times. Fortunately, with the new lung allocation system (LAS) used by the United Network for Organ Sharing (UNOS, www.unos.org) transplant candidates are evaluated based on the severity of their disease. As a result, wait times for transplantation have been dramatically reduced.
Transplantation is not without risk; patients should discuss all of the potential risks and benefits of lung transplantation with their physician.
TREATMENT OF ACUTE EXACERBATIONS AND COMORBIDITIES
Patients with PF can experience periods of worsening called acute exacerbations. High-dose prednisone is usually prescribed for these episodes.2 Your doctor may provide prednisone or other treatments if you have an acute exacerbation.
Patients with PF frequently have other associated conditions, called comorbidities, as well. These can include pulmonary hypertension, GERD, obesity, emphysema, and obstructive sleep apnea. Your treatment plan will likely include both treatments that are directed at your PF and treatments for your comorbidities. Your care providers will help you determine how your comorbidities should be treated.
Since there are currently no FDA-approved therapies to treat IPF in the United States, and limited treatment options in the EU, Canada, and Asia, many patients choose to participate in clinical trials after consulting with their physician. New, experimental therapies are tested for their effectiveness through clinical trials.
The research community is aggressively investigating new treatments for all forms of PF. While the long-term goal of research is to prevent and cure the disease, present therapeutic approaches consist of attempts to slow disease progression and to extend the life expectancy of PF patients. While some studies are in advanced stages of development, others are in much earlier stages. There are a variety of clinical trials that are actively seeking the participation of patients. Some of the therapeutic approaches currently being studied include:
- Pulmonary vasodilators (such as sildenafil), which may aid in processing oxygen more efficiently.
- Anti-fibrotic therapies, which may slow or inhibit the production of scar tissue (fibrosis).
- Inhibitors of tumor angiogenesis, which block the signaling pathway of proteins shown to promote fibrotic proliferation.
- Inhibitors of “growth factor” proteins, which block proteins that can contribute to the formation of fibrosis.
- Genetic research to identify genes and genetic variants that may be associated with the development and progression of PF.
- Biomarker research looking for biologic molecules in the blood, tissue, or other body fluids that may predict the development of PF, rate of disease progression, or efficacy of a therapeutic intervention.
It is very important that patients discuss the possibility of participating in a clinical trial with their physician upon diagnosis. It is through clinical trials that a cure for the disease will be found. Please visit the research section of our website at www.pulmonaryfibrosis.org/research to learn more about clinical trials.
This information has been approved by Gregory P. Cosgrove, MD (September 2012)