What is the treatment approach for interstitial lung disease (ILD) exacerbation?

From the Guidelines

The treatment approach for interstitial lung disease (ILD) exacerbation should be guided by the specific underlying systemic autoimmune rheumatic disease (SARD), with glucocorticoids conditionally recommended as a first-line ILD treatment for people with SARD-ILD other than SSc-ILD, as stated in the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline 1. For people with SSc-ILD, nintedanib is conditionally recommended as a first-line ILD treatment option, whereas for those with IIM-ILD, JAK inhibitors (JAKi) and calcineurin inhibitors (CNIs) are conditionally recommended as first-line ILD treatment options 1. The treatment strategy should prioritize minimizing morbidity, mortality, and improving quality of life, taking into consideration the unique characteristics of each SARD-ILD subtype and the need for a multidisciplinary approach integrating both pulmonary and rheumatological perspectives 1. Key considerations in managing ILD exacerbations include:

• Early recognition and prompt initiation of treatment to prevent irreversible lung damage
• Use of high-dose corticosteroids, such as prednisone, as the cornerstone therapy for most SARD-ILD subtypes
• Administration of supplemental oxygen to maintain adequate oxygen saturation
• Empiric use of broad-spectrum antibiotics to cover potential infectious triggers
• Supportive care, including bronchodilators, careful fluid management, and deep vein thrombosis prophylaxis for hospitalized patients
• Consideration of immunosuppressive agents, such as cyclophosphamide, mycophenolate mofetil, or rituximab, for refractory cases
• Cautious approach to mechanical ventilation due to high mortality rates in ILD patients. It is essential to note that the treatment approach may vary depending on the specific SARD-ILD subtype, and healthcare providers should be aware of the latest guidelines and recommendations, such as those provided by the 2023 ACR/CHEST guideline 1.

From the FDA Drug Label

The efficacy of pirfenidone was evaluated in patients with IPF in three phase 3, randomized, double-blind, placebo-controlled, multicenter trials (Studies 1,2, and 3).

The treatment approach for interstitial lung disease (ILD) exacerbation is not directly addressed in the provided drug label. However, the label discusses the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF), a type of ILD.

• Key points:
  • Pirfenidone has been shown to reduce the decline in forced vital capacity (FVC) in patients with IPF.
  • The primary endpoint was the change in percent predicted forced vital capacity (%FVC) from baseline to study end.
  • Pirfenidone 2,403 mg/day demonstrated a statistically significant treatment effect compared with placebo in Study 1 and Study 2.
• Clinical decision: While pirfenidone may be used to treat IPF, a type of ILD, the label does not provide direct guidance on the treatment of ILD exacerbation. Therefore, a conservative clinical decision would be to consult other resources or guidelines for the treatment of ILD exacerbation. 2

From the Research

Treatment Approach for Interstitial Lung Disease (ILD) Exacerbation

The treatment approach for ILD exacerbation varies depending on the underlying disease.

• For acute exacerbations of ILD, treatment is often unsatisfactory and prognosis is poor 3.
• In patients with connective tissue disease-associated ILD, immunosuppression is the mainstay of treatment, although data from randomized controlled trials to support specific treatments are lacking 4.
• Immunomodulatory agents, such as corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, and rituximab, are used to treat ILDs other than idiopathic pulmonary fibrosis (IPF) 5.
• Antifibrotic therapy with nintedanib or pirfenidone slows annual forced vital capacity (FVC) decline in individuals with IPF, scleroderma-associated ILD, and progressive pulmonary fibrosis of any cause 6.
• Lung transplant may be considered for patients with advanced ILD, and it can improve symptoms and resolve respiratory failure 6, 7.

Management of Acute Exacerbations

• The diagnosis of ILD in hospitalized patients requires input from multiple disciplines, and the prognosis of ILDs presenting acutely varies depending on the underlying ILD 7.
• Patients with advanced ILD or acute exacerbation of idiopathic pulmonary fibrosis have poor outcomes, and the mainstay treatment in these patients is supportive care 7.
• Mechanical ventilation should only be used in these patients as a bridge to lung transplantation 7.

Treatment of Underlying Conditions

• For connective tissue disease-associated ILD, treatment strategies vary according to the clinical situation, and immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to connective tissue disease 4.
• Selective pulmonary vasodilators are used to treat pulmonary arterial hypertension related to connective tissue disease 4.
• Comorbidities such as sleep-disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated in patients with ILD 4.