Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis

Abstract Objectives To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. Results In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07–2.81) and 0.07 (95%CI: 0.01–0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26–5.31) and 0.59 (95%CI: 0.08–4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12–13.70) and 3.36 (95%CI: 0.49–23.29); and serious infection = 1.88 (95%CI: 0.76–4.65) and 0.94 (95%CI: 0.28–3.13). Conclusions IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.