Pulse versus Nonpulse Corticosteroid Therapy in Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Multicenter, Randomized Clinical Trial (SAFER).

Abstract

Rationale: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high short-term mortality, yet guidelines weakly recommend corticosteroids without defining dose or duration. Pulse-dose methylprednisolone is widely used despite minimal evidence.

Objectives: To test the superiority of a pulse-dose corticosteroid regimen over a nonpulse regimen with respect to short-term survival in AE-IPF.

Methods: In this randomised, open-label, multicenter trial at eight South Korean university hospitals, adults with AE-IPF were assigned (1:1) to receive either intravenous pulse methylprednisolone (10 mg/kg for 3 days) or nonpulse regimen (1 mg/kg for 7 days), followed by protocolised tapering and maintenance low-dose prednisolone. Primary outcomes were all-cause mortality at 28 and 90 days. Secondary outcomes included intensive care unit admission, use of mechanical ventilation or extracorporeal membrane oxygenation, death or lung transplantation at 28 and 90 days, and adverse events. The trial was registered at ClinicalTrials.gov, NCT04996303.

Measurements and main results: From July 2021 to April 2024, 100 patients were randomised (pulse n = 51; nonpulse n = 49). The pulse regimen did not demonstrate lower 28-day mortality than the nonpulse regimen (10.0% vs. 14.6%; risk difference, -4.6 percentage points; 95% CI, -18.8 to 9.1; P = 0.549) or lower 90-day mortality (24.5% vs. 29.8%; risk difference, -5.3 percentage points; 95% CI, -23.1 to 12.6; P = 0.648). Treating transplantation as a competing event, Fine-Gray analysis did not demonstrate a difference in 90-day mortality. Secondary outcomes were not demonstrably different between groups.

Conclusions: Among adults with AE-IPF, pulse-dose methylprednisolone did not demonstrate improved 28- or 90-day survival compared with a nonpulse corticosteroid regimen.