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Supplements A Managed Care Perspective:Treatment of Idiopathic Pulmonary Fibrosis

Evaluating New Treatment Options

Steven D. Nathan, MD
Data pertaining to nintedanib, compared with other more selective TKIs, demonstrate benefit in terms of patient-important outcomes in IPF, although no overall mortality benefit was seen. Patients should be warned about the AEs associated with nintedanib, specifically diarrhea, to make an informed decision about therapy. Available evidence does not outline optimal duration of therapy, and it remains to be seen how long the treatment effect endures with ongoing drug therapy.6 As noted earlier, a mutual decision between patient/caregiver and treating clinician, with an emphasis on expected benefits, AE profiles, dosing, frequency, drug interactions, and patient preference, is crucial for successful therapy and patient management with either nintedanib or pirfenidone.12

Comparing the Agents, and Should All Patients With IPF Be Treated With Antifibrotics?

Both pirfenidone and nintedanib have been approved by the FDA for treatment of IPF, independent of disease severity. Currently, there is no definitive evidence to preferentially recommend either of these agents over the other.12 One network meta-analysis of RCTs of pirfenidone, nintedanib, and N-acetylcysteine found that of the 3 treatments, only pirfenidone and nintedanib produced a statistically significant slowing in the rate of FVC decline as compared with placebo. An indirect comparison suggested that nintedanib is statistically significantly better than pirfenidone in slowing FVC decline, while mortality rates favored pirfenidone but were not statistically significant. However, of 1076 references in this analysis, 67 were pulled and only 11 studies were included, and limitations to indirect comparisons such as these must be considered.18 In addition, clinical trials combining these agents are ongoing.12,19

A major question remains in IPF therapy: Should antifibrotic agents be administered to all patients with IPF, including those with more than moderate pulmonary impairment? As noted earlier, clinical trials for these novel agents tended to exclude patients with more severe FVC impairment (Table20).20

The effect of nintedanib and pirfenidone is to slow disease progression in IPF, reducing the rate of decline in FVC.6,8,15,20 For those patients with more severe disease, it remains biologically plausible for these drugs to have the same effect on FVC.20 Subgroup analyses of the major trials suggest that both agents had similar salutary effects in patients with both milder or more severe disease.20-22 Because there is no gradient of disease severity in the studies, it could be inferred that similar treatment effects may be seen in those with disease severity that differs from that seen within the limits of the major RCTs. The actual labeling for these agents states simply “...approved for the treatment of IPF,” without mention of disease severity. This could be interpreted as a tacit endorsement to use them beyond the inclusionary and exclusionary criteria of the clinical trial in well-informed patients with well-established IPF as part of individualized, shared decision-making management.20 An algorithm for patient evaluation and potential therapy has recently been proposed. 23


There has been a sea of change in the management landscape of patients with IPF since the approval of the 2 antifibrotic agents. Their availability has raised the bar for an earlier and accurate diagnosis so that the option of therapy can be addressed with patients before significant loss of lung function, which invariably punctuates the course of this deadly disease. While neither drug is a cure, the availability of both represents hope for patients in terms of modulating the disease course. Their successful clinical development also establishes that the disease can be modified, with the further hope for other, more effective therapies in the future.

Author affiliation: Medical Director, Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia.
Funding source: This activity is supported by educational grants from Genentech and Boehringer Ingelheim Pharmaceuticals, Inc.
Author disclosure: Dr Nathan has the following relevant financial relationships with commercial interests to disclose:
  Roche and Boehringer Ingelheim
  Roche and Boehringer Ingelheim
Authorship information: Concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revisions of the manuscript for important intellectual content.
Address correspondence to:
Acknowledgment: Elizabeth Paczolt, MD, FACNM, provided medical writing and editorial support for this manuscript.
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19.      Eight studies found for nintedanib plus pirfenidone (search results). website. Accessed May 15, 2017.
20.      King CS, Nathan SD. POINT: should all patients with idiopathic pulmonary fibrosis, even those with more than moderate impairment, be treated with nintedanib or pirfenidone? Yes. Chest. 2016;150(2):273-275. doi: 10.1016/j.chest.2016.04.034.
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