Cyclophosphamide plus high-dose glucocorticoids did not confer survival benefit in IPF - Healio
September 23, 2021
2 min read
Naccache JM, et al. ALERT: Asthma in adults, in children and ILDs. Presented at: European Respiratory Society International Congress; Sept. 5-8, 2021 (virtual meeting).
Disclosures: Naccache reports receiving grants or research report from Roche and honoraria or consultant fees from AstraZeneca and Boehringer Ingelheim.
In patients with acute exacerbation of idiopathic pulmonary fibrosis, adding IV cyclophosphamide to high-dose glucocorticoids increased mortality at 3 months, researchers reported at the European Respiratory Society International Congress.
"Current guidelines, that have not changed for 10 years, support using high-dose glucocorticoids such as intravenous methylprednisolone pulses. An international working group suggested in 2016 that potential immunosuppressive therapy should be studied in a randomized controlled trial to better evaluate their potential benefit," Jean Marc Naccache, MD, from the department of pulmonology, allergology and thoracic oncology at Groupe Paris Saint-Joseph Hospital, Paris, said during a virtual presentation. "In a recent international survey, around 20% of the participating pulmonologists declared using cyclophosphamide in acute exacerbation of IPF."
Naccache and colleagues conducted a double-blind, placebo-controlled trial to evaluate efficacy and safety of cyclophosphamide pulses in addition to high-dose methylprednisone. The trial included 119 adults with acute exacerbation of IPF from 35 sites in France. Patients were randomly assigned to receive IV cyclophosphamide pulses at 600 mg/m2 (n = 60; mean age, 71 years; 81.7% men) or placebo (n = 59; mean age, 73.2 years; 76.3% men) at days 0, 15, 30 and 60.
The primary outcome was all-cause mortality at 3 months. Secondary outcomes included overall survival at 6 and 12 months, cause of death at 6 or 12 months, risk factors for mortality at 3 months and safety.
In the intention-to-treat population, the rate of 3-month all-cause mortality was 45% in patients assigned cyclophosphamide plus glucocorticoids compared with 31% in patients who received placebo (P = .1). In the per-protocol population, the rate of 3-month all-cause mortality was 40% vs. 30%, respectively, according to the results.
Mortality at 3 months increased as the severity of acute exacerbation of IPF increased (OR = 2.62; 95% CI, 1.12-6.12). Three-month mortality risk decreased if patients used antifibrotic therapy at baseline (OR = 0.33; 95% CI, 0.13-0.82).
There was no statistically significant difference in overall survival at 12 months, with a survival probability of 40.5% in the cyclophosphamide plus glucocorticoids group vs. 49.5% in the placebo group (log-rank P = .23).
Causes of death between 6 and 12 months were all attributable to respiratory causes, with four deaths in the cyclophosphamide plus glucocorticoids group and five deaths in the placebo group.
When analyzing risk factors for 3-month mortality, researchers observed IPF severity independently of the treatment group was associated with increased mortality (adjusted OR = 2.62; 95% CI, 1.12-6.12; P = .03) and antifibrotic therapy use at baseline was associated with decreased risk for mortality (adjusted OR = 0.33; 95% CI, 0.13-0.82; P = .02).
Similar rates of adverse events occurred in both groups. The most common adverse event was infection, which was reported in 33% of the cyclophosphamide plus glucocorticoids group and 36% of the placebo group.
"Further studies are needed to evaluate the efficacy and safety of glucocorticoids in acute exacerbation of IPF and to find potential targets for innovative treatments in acute exacerbation of IPF," Naccache said.
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