nintedanib can be used to treat fibrotic HP and CTD ILD

The regulatory approval and increasing use of the antifibrotic agents nintedanib, an oral tyrosine kinase inhibitor, and pirfenidone, an oral medication with antiproliferative, antioxidative and anti-inflammatory effects, in patients with idiopathic pulmonary fibrosis (IPF) have led to investigation of these medications in patients with other forms of fibrotic ILD. On the basis of the randomized placebo-controlled INBUILD trial in patients with progressive fibrosing ILD, the United States Food and Drug Administration extended the approval for nintedanib to additional patients with fibrotic ILD, including those with fibrotic hypersensitivity pneumonitis and CTD-related ILD. Patients enrolled in the INBUILD study had evidence of fibrotic ILD based on high-resolution CT (reticulation and traction bronchiectasis with or without honeycomb fibrosis of >10%) and a combination of worsening dyspnea, decline in FVC, and/or worsening fibrosis on chest CT scan over the past 24 months. Mean annual decline in FVC was significantly less (107 mL) in the nintedanib group compared with placebo over 52 weeks. The subsequent SENSCIS trial, a randomized placebo-controlled trial of nintedanib in patients with systemic sclerosis-related ILD, also demonstrated a slowing of the decline in FVC over 12 months.

Numerous investigations of pirfenidone in patients with a variety of forms of fibrotic ILD including unclassifiable ILD, rheumatoid arthritis-related ILD, and systemic sclerosis-related ILD have yet to demonstrate an unequivocal benefit to this treatment, although some trials are still ongoing.

A joint clinical practice guideline from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax for patients with fibrosing ILD with progression has proposed “progressive pulmonary fibrosis” (PPF) as the uniform term. They defined PPF as meeting at least two of the following three criteria: worsening symptoms, radiological progression, and physiological progression, occurring within the past year without another explanation in patients with fibrotic ILD other than IPF. A conditional treatment recommendation (the majority of individuals in this situation would want the suggested course of action, but a sizable minority would not) for the use of nintedanib was made, with a recommendation for additional research into the efficacy of pirfenidone in this patient population.

Data from the Scleroderma Lung Study II supports the use of mycophenolate mofetil, an inhibitor of lymphocyte proliferation, in patients with systemic sclerosis-related ILD, as do data from the focuSSced study of tocilizumab, an anti-interleukin-6 receptor antibody. However, these trials selected for patients with more inflammatory CTD-ILD, and these medications have not been prospectively studied in patients with other forms of progressive fibrotic ILD, including fibrotic hypersensitivity pneumonitis (choices B and D are incorrect).1

Footnotes

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