Pulse vs standard-dose steroids in acute exacerbation of IPF: no survival difference

Design

Open-label, multicentre, randomised trial

Population

100 adults with acute exacerbation of idiopathic pulmonary fibrosis

Primary outcome

All-cause mortality at 28 and 90 days

Effect

28-day 10.0% vs 14.6% (RD -4.6, 95% CI -18.8 to 9.1); 90-day 24.5% vs 29.8%

SAFER was an open-label randomised trial at eight South Korean university hospitals. It assigned 100 adults with acute exacerbation of idiopathic pulmonary fibrosis to intravenous pulse methylprednisolone, 10 mg/kg for 3 days, or a non-pulse regimen of 1 mg/kg for 7 days, both followed by protocolised tapering and low-dose maintenance.

Mortality at 28 days was 10.0% with pulse dosing and 14.6% without (risk difference -4.6 points, 95% CI -18.8 to 9.1), and at 90 days 24.5% against 29.8% (-5.3 points, -23.1 to 12.6). Neither difference was significant, and ICU admission, ventilation and other secondary outcomes were similar.

Pulse methylprednisolone is widely used for these exacerbations on little evidence; guidelines suggest corticosteroids only weakly and without a dose. This is the first randomised comparison of dose, and it found no clear advantage for the higher one. With only 100 patients it cannot exclude a moderate benefit or harm, so it does not settle the question, but it removes any evidence-based reason to insist on pulse dosing.

• Pulse methylprednisolone did not improve 28- or 90-day survival over 1 mg/kg in this trial.
• Consider a non-pulse regimen, especially where steroid toxicity is a concern.
• Guidelines have not changed and still recommend corticosteroids only weakly in acute exacerbation.
• Discuss prognosis and ceilings of care early; 90-day mortality was about 1 in 4.
• Look for infection, heart failure and pulmonary embolism as alternative causes of deterioration.

Why it matters

It challenges the reflex use of pulse methylprednisolone, which carries real toxicity in older, frail patients.

Don't overread it

Only 100 patients and open-label; the confidence intervals are wide enough to include meaningful benefit or harm.

The statistics, in plain English

The 90-day risk difference of -5.3 points has a confidence interval from -23.1 to 12.6: pulse dosing could plausibly reduce deaths by 23 points or increase them by 13. That means the trial is inconclusive rather than showing the two are equal.

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