From the Guidelines
Recent advances in management of Interstitial Lung Disease (ILD) prioritize a personalized approach, focusing on disease-modifying therapies, such as nintedanib and pirfenidone, alongside targeted immunosuppression and supportive interventions to improve morbidity, mortality, and quality of life. The most recent and highest quality study, published in 2024 by the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) 1, provides a guideline for the treatment of ILD in people with systemic autoimmune rheumatic diseases, emphasizing co-management by rheumatologists and pulmonologists.
Key Therapies for ILD
- Antifibrotic medications: Nintedanib (150mg twice daily) and pirfenidone (801mg three times daily) are cornerstone therapies for idiopathic pulmonary fibrosis and are now used in other progressive fibrosing ILDs, as supported by studies such as the SENSCIS trial 1 and the INBUILD trial.
- Immunosuppression: Targeted immunosuppression has evolved to include mycophenolate mofetil (1-1.5g twice daily), rituximab (typically two 1g infusions separated by two weeks), and JAK inhibitors like tofacitinib, with evidence from studies like the SLS II trial and the RECITAL trial 1.
- Supportive interventions: Pulmonary rehabilitation programs, oxygen therapy for resting or exertional hypoxemia, and management of comorbidities like GERD are essential for improving quality of life and reducing morbidity, as highlighted in the guideline 1.
Personalized Approach to ILD Management
The guideline emphasizes the importance of shared decision-making, considering factors such as ILD severity, risk factors for progression, other disease manifestations, cost, and toxicity when choosing a medication. Co-management with pulmonologists is advised for initiation of ILD treatment, particularly to determine the need for treatment in asymptomatic patients with stable and mild ILD.
Future Directions
Research is needed to better understand fibrotic, inflammatory, or mixed lung phenotypes and to develop predictive biomarkers, which could lead to more informed management decisions. Higher-certainty evidence is needed on the impact of therapeutics on patient-important outcomes, including harms, as noted in the 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).
Study 1 was a 52-week trial comparing pirfenidone 2,403 mg/day (n=278) versus placebo (n=277) in patients with IPF
Study 2 and Study 3 were nearly identical to each other in design, with few exceptions, including an intermediate dose treatment arm in Study 2.
The primary endpoint was the change in percent predicted forced vital capacity (%FVC) from baseline to study end, measured at 52 weeks in Study 1, and at 72 weeks in Studies 2 and 3
The recent advances in management of Interstitial Lung Disease (ILD), specifically Idiopathic Pulmonary Fibrosis (IPF), include the use of pirfenidone.
- Pirfenidone has been shown to reduce the decline in Forced Vital Capacity (FVC) in patients with IPF, as demonstrated in Study 1 and Study 2.
- The treatment effect of pirfenidone on FVC was statistically significant in Study 1 and Study 2, but not in Study 3.
- Pirfenidone may be a useful treatment option for patients with IPF, as it has been shown to slow the progression of lung function decline 2.
- However, all-cause mortality did not show a statistically significant difference between pirfenidone and placebo in the studies.
From the Research
Recent Advances in Management of Interstitial Lung Disease (ILD)
- The management of ILD has seen significant advancements in recent years, with a focus on the use of antifibrotic agents such as Pirfenidone and Nintedanib 3, 4.
- These drugs have been shown to reduce the rate of decline in forced vital capacity (FVC) and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis (IPF) 5.
- Pirfenidone and Nintedanib have been extensively validated, but some patients reported several side effects, predominantly gastrointestinal symptoms, as well as photosensitivity and skin rashes 3, 6.
Efficacy of Pirfenidone and Nintedanib in ILD
- Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies 4.
- A systematic review summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis, as well as ongoing and upcoming clinical trials 4.
- The results of the review showed that nintedanib demonstrated efficacy in slowing disease progression in patients with interstitial lung diseases other than IPF, while results on the use of pirfenidone should be interpreted with caution due to trial limitations 4.
Safety and Tolerability of Combination Therapy
- A 24-week, single-arm, open-label, phase IV study assessed the safety and tolerability of treatment with pirfenidone and nintedanib in patients with IPF, and found that combined use was tolerated by the majority of patients with a similar pattern of treatment-emergent adverse events expected for either treatment alone 6.
- However, a randomised controlled trial found that combination therapy with pirfenidone plus inhaled N-acetylcysteine resulted in worse outcomes for IPF, with a higher rate of decline in FVC compared to pirfenidone alone 7.
Future Directions
- Further research is needed to optimize the use of antifibrotic agents in patients with ILD, which could slow disease progression and decrease all-cause mortality 3, 4.
- Several randomized control trials are underway to improve the quality of evidence in the ILD field, and to establish the treatments that can stop ILD progression 4.