Pirfenidone Linked to Reduced Pulmonary Fibrosis Risks Versus Nintedanib

May 17, 2020

New cohort data comparing the lone regulated IPF therapies show one is associated with reduced mortality—while the other has a better continuation of care.

Vincent Cottin

Pirfenidone (Esbriet) bettered nintedanib (Ofev) in mortality risk and respiratory-related hospitalizations among treated patients with idiopathic pulmonary fibrosis (IPF) over a 12-month assessment.

However, fewer patients with IPF treated with nintedanib—recently bolstered in its regulatory indications—discontinued care than those on pirfenidone.

The findings, planned for presentation at the American Thoracic Society (ATS) 2020 International Conference this year, show a potential disparity of efficacy between the only 2 therapies approved by the US Food and Drug Administration (FDA) for treating IPF.

A team of international investigators, led by Vincent Cottin, MD, PhD, of the National Reference Coordinating Center for Rare Pulmonary Diseases and Louis Pradel Hospital in France, sought to assess all-cause mortality and acute-respiratory related hospitalizations among patients receiving either therapy or none at all.

Both therapies were approved by the FDA for IPF in October 2014. Prior to their indication, the only treatment options for the chronic, irreversible, and ultimately fatal disease included oxygen therapy, pulmonary rehabilitation, and eventually, lung transplant.

In early March, the FDA approved oral nintedanib for the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype—a first-of-its-kind indication.

Cottin and colleagues conducted a cohort analysis using the French National Health System claims data, including patients diagnosed with IPF aged ≥50 years old between January 2015-December 2016.

The team estimated for cumulative incidence rates for untreated and newly-treated patients on either pirfenidone or nintedanib. They compared all-cause mortality, acute respiratory-related hospitalizations, and treatment discontinuation among each therapy using a Cox proportional hazards model adjusted for confounders.

Investigators identified 7194 patients with IPF in the claims data. Among them, 521 (7.2%) were excluded, as they were not newly-treated patients. Another 5306 (74.5%) remained untreated; 804 (11.2%) initiated pirfenidone and 509 (7.1%) initiated nintedanib.

Cumulative, non-adjusted, all-cause mortality at 3 years was 50.23% (95% CI, 48.34-52.09) in untreated patients, 25.5% (95% CI, 19.6-31.7) in patients who initiated pirfenidone, and 31.1% (95% CI, 21.2-41.6) in patients who initiated nintedanib.

After adjusting for confounders including index date patient age, gender, year, time since IPF diagnosis, and proxies of disease severity identified in the previous 12 months, the team confirmed nintedanib was associated with greater all-cause mortality (HR, 1.80; 95% CI, 1.25-2.60) and acute respiratory hospitalization (HR, 1.32; 95% CI, 1.01-1.73) risks than pirfenidone.

At the same time, nintedanib was associated with a significantly lower risk of treatment discontinuation at 12 months than pirfenidone (HR, 0.72; 95% CI, 0.60-0.86).

Investigators noted limitations of the cohort including the observational design of the study. That said, there were distinct disparities to draw on the effect of either IPF drug since both reached the market a half-decade ago.

“Compared to nintedanib, pirfenidone was associated with lower risks of death and acute respiratory-related hospitalizations but with a higher risk of treatment discontinuation at 12 months,” they wrote. “These findings suggest possible differences in effectiveness between available drugs for IPF.”

The study, “Outcomes in Patients Receiving Nintedanib or Pirfenidone for Idiopathic Pulmonary Fibrosis,” was published online by ATS.