Cyclophosphamide added to steroids increases mortality in acute exacerbation of IPF: Lancet

The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle.

The results of the study are as follows:

· Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis.

· The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group.

· Similar results were found after adjustment by IPF severity.

· The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF and was lower with the use of antifibrotic therapy.

· Adverse events were similar between groups by 6 months and their proportion, including infections, did not differ.

· Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group.

Thus, the researchers concluded that in patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients.

Reference:

Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial Naccache J et. al published in The Lancet: Respiratory Medicine

DOI: https://doi.org/10.1016/S2213-2600(21)00354-4