Intravenous pulse doses of high-dose corticosteroid and cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis

Acute Exacerbation (AEx) is a frequent complication of Idiopathic Pulmonary Fibrosis (IPF) associated with high mortality. To date there is no evidence-based therapy for AEx of IPF (AEx-IPF). Our aim was to evaluate the effectiveness in terms of survival of intravenous pulse doses of high-dose corticosteroid and cyclophosphamide in a cohort of patients with AEx-IPF. We performed a retrospective analysis on patients with AEx-IPF referred to the Respiratory Unit at San Gerardo hospital, Monza, Italy, from 2009 to 2013. AEx-IPF diagnosis was made according to Collard criteria (Collard HR et al , AJRCCM 2007; 176:636–43). All patients were treated with daily pulse doses of methylprednisolone (1000 mg) for three days, followed by monthly pulse doses of cyclophosphamide (600mg/m 2 of body surface area, maximum dose 1 g) in association with maintenance-dose of oral prednisone (0.5 mg/kg). We identified 11 patients with AEx-IPF (7 males, median age 68 years). A median of 4 monthly pulse doses of cyclophosphamide were administered. Overall survival at 3 months was 73%, at 6 months 63%, at 12 months 55%, at 18 months 45% and at 2 years 27%. Six patients died because of respiratory failure. A patient died because of breast cancer and one due to lung cancer. Overall survival in our cohort is better compared to the ones reported in patients not treated with systemic immunosuppressive therapy (Song JW et al , ERJ 2011; 37:356–363). Immunosuppressive agents, such as cyclophosphamide, in addiction to high-dose corticorteroids might improve short- and long-term outcomes of AEx-IPF. Randomized-controlled trials on large cohorts of patients are needed to confirm our observation.