This forum houses frequently asked questions related to IPF with answers from the expert faculty.

 

 

 flaherty-icon-main  

Dr. Kevin Flaherty, MD, MS answers common questions related to the newly approved treatments for IPF

Kevin Flaherty, MD, MS, University of Michigan Health System

  1. The primary efficacy results for pirfenidone and nintedanib seem to be quite close. What are the main safety considerations for each drug and how do these guide the choice for an individual patient?
    Listen Listen

  2. What are the major considerations for adding pirfenidone or nintedanib to multiple medications that many of my patients are already on?
    Listen Listen

  3. How will the recent drug approvals change the role of ILD centers?
    Listen Listen

  4. Some of my patients have received other medications for IPF. If they are stable on NAC or corticosteroids should I switch to one of the newly-approved drugs?
    Listen Listen

  5. How do the drug approvals impact lung transplant decisions?
    Listen Listen

  6. Should we prescribe nintedanib or pirfenidone for patients with advanced IPF?
    Listen Listen

 nathan  

Based on a discussion including Dr. Steven Nathan, Dr. A. Whitney Brown, Dr. Marilyn Glassberg, Dr. Kevin Flaherty, Dr. Kevin Leslie and Dr. Paul Noble

Edited by Steven D. Nathan, MD, Medical Director, Lung Transplant Program Director, Advanced Lung Disease Program, Inova Fairfax Hospital, Falls Church, Virginia

1. How do we decide between pirfenidone and nintedanib for patients with IPF?

The efficacy of each of these drugs was similar in the recently published clinical trials (ASCEND and INPULSIS), and both are FDA-approved for the treatment of IPF.  Side effects are the primary differences that we know about. It is important to stress that patients should be involved in the decision process as lifestyle, pill burden, and side effect tolerance will vary considerably. Comorbidities and reconciliation with other medications should also be considered. 

2. How will the side effect profiles and dosing impact treatment decisions?

Head-to-head efficacy data with pirfenidone and nintedanib are not available. Published evidence suggests similar efficacy of nintedanib and pirfenidone, so side effects and pill burden are the major considerations. The prescribing information for these drugs (http://www.accessdata.fda.gov/) describes the side effects observed in the pivotal clinical trials as well as warnings and precautions. Both drugs have a risk of liver enzyme elevation. Pirfenidone is associated with rash, photosensitivity, and nausea; nintedanib is associated with diarrhea. (Loperamide may be useful in managing diarrhea, which tends to diminish with time.) While dose reduction may address side effects, efficacy at lower doses of either drug has not been well documented. Liver function tests are recommended for both drugs prior to treatment and periodically during therapy (refer to prescribing information for recommended intervals). Ongoing discussions with patients are critical, as patients who do not tolerate side effects or dosing regimens may not adhere to the regimen.

3. How do you know the treatment is working? When should a switch be considered?

Nintedanib and pirfenidone have been shown in clinical trials to slow the rate of decline of FVC in patients with IPF. Lung function cannot be expected to improve as a result of treatment with these drugs, and at this time it is also impossible to say whether they are effective in an individual patient since the natural course of IPF is variable and unpredictable. There are no validated biomarkers to predict the disease course or the medication response for an individual patient. Decreased lung function does not necessarily suggest that drug therapy is ineffective. Switching from one treatment to the other can be considered if the practitioner suspects treatment failure. Another option is combining pirfenidone and nintedanib, but there is no evidence that this approach is effective. Available data do not support discontinuation of IPF treatment, and the PILOT experts recommend treatment of IPF with at least one drug if the side effects are tolerable, even in the face of disease progression. Referral to an ILD center may be considered for complicated patients) http://www.pulmonaryfibrosis.org/life-with-pf/find-medical-care).

4. If I am not sure about a diagnosis of IPF should I consider empiric corticosteroids?

The therapeutic approach should be dictated by the diagnosis. While some patients with ILD may respond to corticosteroids, the 2011 ATS/ERS guidelines recommend against their use for IPF. Patients with ILD should be worked up with a physical exam, history, and HRCT. Other causes of the ILD should be explored such as connective tissue disorders, nonspecific interstitial pneumonia, and chronic hypersensitivity pneumonitis. Serologic panels can help with this differential and a lung biopsy may be useful for patients with a possible UIP finding on HRCT. In some cases a definitive diagnosis cannot be made; for such patients the corticosteroid approach should be considered on an individual basis. Diagnosis of specific ILDs can be challenging and early referral to specialty ILD centers can be of great benefit to the patient (http://www.pulmonaryfibrosis.org/life-with-pf/find-medical-care).

5. Can nintedanib and pirfenidone be used together as dual therapy?

Safety, PK, and efficacy studies have not been done with a combination of nintedanib and pirfenidone. Although the mechanism of action of these drugs in lung fibrosis is not completely elucidated it is believed that they work through different mechanisms and their effects could potentially be additive or synergistic. Considerations for discussion with the patient include drug-drug interactions, side effects, payment, and lack of clinical evidence for efficacy and safety of dual therapy.


Associate Professor of Medicine
Division of Pulmonary and Critical Care Medicine
Director of the Interstitial Lung Disease Program
University of California, San Francisco
San Francisco, California


Associate Professor of Pulmonary and Critical Care Medicine
University of Michigan Health System
Ann Arbor, Michigan


Nina Ireland Distinguished Professor of Clinical Medicine and Surgery
University of California, San Francisco
San Francisco, California


Professor of Pathology
Mayo Clinic College of Medicine

Rochester, Minnesota,
Consultant in the Department of Laboratory Medicine and Pathology
Mayo Clinic
Scottsdale, Arizona


Medical Director of the Advanced Lung Disease Program
Director of the Lung Transplant Program
Inova Fairfax Hospital
Falls Church, Virginia


Associate Professor of Medicine
Department of Pulmonary and Critical Care Medicine
Director of Outpatient Medical Education
Director of the ILD Clinic
University of Chicago Hospitals and Clinics
Chicago, Illinois


Professor of Medicine
Medical Director of the Lung and Transplant Program
Director of the Advanced Lung Disease/ILD Program
Mount Sinai School of Medicine
New York, New York


Professor of Pulmonary Medicine
Division of Pulmonary and Critical Care Medicine
Medical University of South Carolina
Charleston, South Carolina

Access other Therapeutic Areas: