Complexity of PF-ILD Creates Detection, Treatment Challenges

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Presenters at CHEST 2020 discussed the concept of how patients with interstitial lung disease (ILD) can develop a progressive fibrosis phenotype and how providers can detect and treat these patients.

Early recognition of an interstitial lung disease (ILD) phenotype is critical to finding effective treatments for patients and to prevent the disease from developing into a progressive fibrosing (PF) phenotype, according to presenters during a session at CHEST 2020.

ILD can be acute, meaning that it’s caused by an external antigen, or chronic, meaning that it is a slow progression of a worsening condition. PF-ILD is characterized by increased fibrosis in high-resolution computed tomography (HRCT) scans, worsening respiratory symptoms and quality of life, declining lung function, and higher rates of mortality than patients without thus phenotype despite receiving therapy.

Sonye Danoff, MD, PhD, an associate professor of the Medicine Division of Pulmonary and Critical Care Medicine and co-director at Johns Hopkins ILD/PF Program, said during the session that the most important step in diagnosing ILD is to determine its etiology, and she discussed the thorough history (medical, social, environmental) that should be taken in order to rule out other conditions.

Many patients with ILD have an underlying connective tissue disease, such as scleroderma, limited cutaneous systemic sclerosis, rheumatoid arthritis, polymyositis, dermatomyositis, antisynthetase syndrome, or Sjogren syndrome.

According to presenter Kristin Highland, MD, the director of Pulmonary Medicine for the Rheumatic Lung Disease Program at the Cleveland Clinic in Ohio, up to >90% of patients with scleroderma, 90% of patients with antisynthetase syndrome, and 30% to 76% of patients with rheumatoid arthritis will develop clinically significant ILD.


“For some patients…all of the standard approaches [to treatment] are not working and, instead, what's happening is that they're being driven towards this fibrotic phenotype. That appears to be a process which occurs even in the presence of all of the appropriate therapeutic agents and interventions,” said Danoff.

Danoff and Highland presented 2 case studies of different patients that both eventually were classified as having PF-ILD.

Danoff’s case was a 69-year old White man with dyspnea on exertion that was progressively getting worse. The man had no symptoms of heart failure and no acute infections. His chest x-ray showed upper lobe intestinal changes and air trapping.

After diagnosing a patient with hypersensitivity pneumonitis, Danoff reviewed his environment and found that antigens stemming from pet birds were present in the home.

After the birds were removed, he got better, but then worsened again when his spouse brought home a new down comforter, which turned out to be another environmental antigen. Although the down comforter was removed, the man’s symptoms continued to worsen, suggesting that a PF phenotype had developed.

Highland’s case was a 46-year-old African American man with a history of progressive shortness of breath, mild hypertension, and a nonproductive cough. He was a nonsmoker with a job that had reduced exposure to potential antigens. He also had Raynaud's phenomenon. After reviewing physical exams, CT scans, and lab results, which included the presence of autoantibodies against topoisomerase I (anti-Scl 70 antibodies) Highland diagnosed the man with scleroderma.

Noting her patient had 3 risk factors for progressive sclerodema (positive for anti-Scl 70, Black, and Raynaud’s) Highland then moved on to treatment options and reviewed emerging therapies.

Treatment could include monotherapy or combination therapy, especially for patients with progressive conditions. Monotherapy can consist of nintedanib if CT scans do not present ground glass opacities or mycophenolate mofetil or cyclophosphamide if they do.

Combination therapy can consist of a mixture of all 3 drugs. Highland said that pulmonary function testing should continue regardless of physician therapy choice.

Highland also reviewed recent trials for 2 approved antifibrotic therapies, nintedanib (Ofev) and pirfenidone (Esbriet).

In a phase 3 trial for nintedanimb (SENSCIS), the annual rate of decline in forced vital capacity was slower in the treatment group compared with the placebo group over 52 weeks (−52.4 ml per year in the nintedanib group and −93.3 ml for the placebo).

A similar study (INBUILD) looking at nintedanimb for PF-ILD also found a significantly reduced rate of decline in FVC.and stayed that way.

A phase 2 trial of pirfenidone for unclassifiable PF-ILD found primary endpoints could not be met but secondary analyses indicated that there might be some benefit and that research should continue.