Objectives: Current guidelines suggest treating poor-prognosis eosinophilic granulomatosis with polyangiitis (EGPA) with a combination of glucocorticoids (GCs) plus cyclophosphamide (CYC). However, there is little data to support the need for the addition of CYC. The objective of this study was to compare GCs plus CYC to GCs alone as induction therapy in poor-prognosis EGPA. Methods: We emulated a target trial using observational data from a European multicenter retrospective database. We included patients with newly diagnosed EGPA with a 1996 Five Factor Score (FFS) of at least 1, treated with GCs or GCs plus CYC between June 1985 and November 2018. Propensity score analysis was used to adjust for potential confounders. Primary outcome was relapse at 12months. Secondary outcomes included major relapse at 12months and GC-dependent asthma and/or ear nose and throat (ENT) manifestations at 24months. Results: A total of 209 patients were included: 47 % were male and the mean age at diagnosis was 52 (±16 years); 26 % were treated with GCs alone and 74 % with GCs plus CYC. After adjustment, the risk of relapse (hazard ratio [HR]: 0.24, 95%CI [0.08–0.67], p = 0.007), major relapse (HR: 0.24, 95%CI [0.07–0.85], p = 0.026) and the proportion of GC-dependent asthma and/or ENT manifestations (odds ratio:0.30, 95%CI [0.14–0.66], p = 0.003) were lower in the GCs plus CYC group compared to the GCs alone group. Conclusion: This target trial emulation study shows that the addition of CYC to GCs reduces the risk of vasculitis relapse and the rate of GC-dependent asthma and/or ENT manifestations in patients with poor-prognosis EGPA.
