Background Although concomitant use of cyclophosphamide (CYC) with glucocorticoids (GC) is considered to be one of the standard remission-induction therapies for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis over 30 years,… Click to show full abstract
Background Although concomitant use of cyclophosphamide (CYC) with glucocorticoids (GC) is considered to be one of the standard remission-induction therapies for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis over 30 years, there are few reports about clinical efficacy or effectiveness of CYC. Objectives To evaluate effectiveness and safety of concomitant CYC as remission induction therapy in Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) using data sets from two nationwide prospective cohort studies. Methods Newly diagnosed MPA and GPA patients treated with GC with or without CYC for remission-induction therapy were enrolled. The patients treated with other immunosuppressants or plasma exchange were excluded. A propensity score for the use of CYC was estimated using age, types of AAV, serum creatinine level, Birmingham Vasculitis Activity Score (BVAS), and initial GC dosage at baseline. After propensity score matching at 1:1, remission, overall survival, and end-stage renal disease (ESRD)-free survival rates, Vasculitis Damage Index (VDI), and incidence of serious infection within 6 months were compared between patients treated with and without concomitant CYC. Results Of enrolled 327 patients, concomitant CYC was used in 119 (36%) patients during the initial 3 weeks of treatment. After propensity score matching, 95 patients with concomitant CYC (CYC group) and 95 controls (non-CYC group) were selected. Demographics, baseline characteristics and treatments were balanced between the two groups except for myeloperoxidase ANCA positivity (Table). The remission within 6 months was achieved in 85% in both groups. The survival and ESRD-free survival rates were also similar between the two groups (log-rank test; p=0.77 and 1.0, respectively). Median VDI at the time of last observation did not differ between the two groups (CYC, 3 [interquartile {IQR}: 2–4]; non-CYC, 2 [IQR:1–3], p=0.26). The accumulated GC dosage of the CYC-group from 3 to 24 months was lower than the non-CYC group, the GC-related damage did not differ (CYC, 1 [IQR: 0–2]; non-CYC, 0 [IQR:0–2], p=0.69). Table. Comparison of patients treated with concomitant cyclophosphamide and with glucocorticoid alone Variables at baseline and treatments Cyclophosphamide users(n=95) Non-users(n=95) p-value Male/female, n 51/44 (46%) 60/35 0.24 Age, years 70 (65–78) 71 (62–75) 0.92 GPA/MPA 26/69 27/68 1.0 Myeloperoxidase ANCA, n (%) 78 (82) 89 (94) 0.02* Proteinase-3 ANCA, n (%) 17 (18) 8 (8) 0.15 Serum creatinine, mg/dL 1.2 (0.8–3.2) 1.1 (0.7–2.5) 0.39 C-reactive protein, mg/dL 7.5 (2.3–12.6) 7.2 (2.1–11.7) 0.35 BVAS 15 (12–20) 16 (12–21) 0.99 Interstitial lung disease, n (%) 38 (40) 37 (49) 0.55 Glucocorticoid (mg/kg/day) d 0.83 (0.72–0.97) 0.83 (0.67–0.99) 0.89 Values expressed as a number of patients (%) or median (interquartile). *p<0.05. Conclusions In Japanese patients with MPA and GPA, concomitant CYC could not show any benefits on clinical outcomes within 24 months. Dosage and treatment duration of CYC, as well as tapering methods of GC, could be confounding factors. Longer observation may be necessary to confirm the effectiveness of CYC as GC sparing agent. Disclosure of Interest None declared
               
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