This issue features a pro/con debate on the new IPF treatments, a review of a challenging treatment case, and further IPF treatment Q&A.

Marilyn Glassberg, MD; Charlie Strange, MD, FCCP and Imre Noth, MD




In This Issue:

1. Pro/Con Debate

2. Treatment Dilemmas
  3. IPF Treatment Q&A

4. Request Meeting


Dr. Marilyn Glassberg and Dr. Charlie Strange's debate


Listen to Dr. Glassberg and Dr. Strange discuss how they choose a treatment for a patient with IPF. Using a pro/con format, they address the efficacy, safety, and side effects of new drugs and the important role comorbidities play when making treatment decisions.


A challenging treatment case


Treatment Case: Harrison
Click to view Dr. Noth’s systematic approach to treating a challenging case.

Imre Noth, MD, The University of Chicago Medicine


Expert responses to common questions


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 ( 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)

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 (

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.

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