Comparison between Rituximab and Cyclophosphamide in Treatment of ANCA-Associated Vasculitis on Remission Induction: A Meta-Analysis

Research Article

Austin J Nephrol Hypertens. 2021; 9(1): 1103.

Comparison between Rituximab and Cyclophosphamide in Treatment of ANCA-Associated Vasculitis on Remission Induction: A Meta-Analysis

Kena Wang¹, Yongchen¹ and Jiayun Xu²*

¹College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China

²Department of Endocrinology and Metabolism, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China

*Corresponding author: Jiayun Xu, Department of Endocrinology and Metabolism, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, Henan, China

Received: February 17, 2022; Accepted: March 10, 2022; Published: March 17, 2022


Objectives: Currently, immunosuppressants including cyclophosphamide and azathioprine are the main treatment options for anti-neutrophil associated vasculitis. However, since cyclophosphamide may cause serious adverse reactions, it is necessary to explore for a new drug, and rituximab is one option with less adverse reaction. There are a few studies on rituximab versus cyclophosphamide in the treatment of antineutrophil associated vasculitis. The meta-analysis is carried out to evaluate the efficacy of rituximab, compared with cyclophosphamide, as a remission induction therapy in AAV.

Methods: Firstly we searched a Chinese database (CNKI, Wanfang) and English databases (Pubmed, Cochrane Library, Embase) according to inclusion criteria and exclusion criteria before October, 2021. Then Revman5.4 and Stata were used for data analysis which was then integrated by fixed effects or random effects.

Results: After browsing the full texts, we finally included 7 eligible articles, involving 737 patients in total. With Revman5.4 software, we could draw the following conclusions: 6-month complete response rate (Chi²=0.46, df=1 P=0.50 I²=0%), 12-month complete response rate (Chi²=0.31 df=1 P=0.58 I²=0%), 18-month complete response rate (Chi²=0.18 df=1 P=0.67 I²=0%). Adverse event (Chi²=3.15 df=4 P=0.53 I²=0%), respectively for reached primary endpoint, failed primary endpoint in contrast. The result showed (Chi²=3.29 df=3 P=0.35 I²=9%, Chi²=1.72 df=2 P=0.42 I²=0%), 6-momth relapse, 12-momth relapse, 18-month relapse (Chi²=0.22 df=1 P=0.64 I²=0%, Chi²=0.04 df=2 P=0.98 I²=0%, Chi²=0.13 df=1 P=0.72 I²=0%), GPA 0f 6-month (Chi²=0.47 df=1 P=0.50 I²=0%), MPA of 6-month (Chi²=1.52 df=1 P=0.22 I²=34%). The above data are statistically significant.

Conclusion: Based on the above data, we can conclude that compared with cyclophosphamide, rituximab can play a certain role in the treatment of ANCA disease, improve the complete response rate, reduce the rate of adverse reactions and recurrence, and is expected to replace cyclophosphamide as a first-line drug in clinical practice.

Keywords: Rituximab; Cyclophosphamide; ANCA-Associated Vasculitis; Remission induction; Meta-analysis


ANCA-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum, mainly involving small blood vessels (arterioles, arterioles, venules, and capillaries) and middle and small arteries as well. Including microscopic polyvasculitis, granulomatous polyvasculitis and eosinophilic granulomatous polyvasculitis are mainly related to genetic factors and infection, especially bacterial infection and morbidity. The pathological changes are characterized by full-thickness inflammation and necrosis of small blood vessels with or without granulomatous formation. Close attention shall be paid to cellulate-like necrosis and infiltration of neutrophils, lymphocytes, and eosinophils. The treatment of ANCArelated vasculitis can be divided into two stages: induced remission and maintenance remission. The induced remission is usually sufficient glucocorticoid, combined with immunosuppressive therapy, CTX is most commonly used, and the maintenance remission is mainly lowdose glucocorticoid, combined with immunosuppressive therapy, such as azathioprine and methotrexate.

Cyclophosphamide (CYC) has been widely used in induction therapy for AAV for decades with a remission rate of 70-90% [1,2]. However, CYC leads to many serious acute side effects, such as haemorrhagic cystitis, tumors of the urinary bladder, infertility, and bone marrow depression [3]. Therefore, it is necessary to explore for new agents with similar efficacy but less toxicity.

Rituximab is a B-cell-depleting anti-CD20 monoclonal antibody that has been approved by the European Medicines Agency and the U.S. Food and Drug Administration for the treatment of non Hodgkin’s lymphoma [4] and rheumatoid arthritis [5-8]. In ANCAassociated vasculitis, B-cell activation and levels of B-cell-activating factor correlate with disease activity [9,10]. Cyclophosphamide suppresses the activation, proliferation, and differentiation of autoreactive B cells [11]. The pathogenic role of B-cells and ANCA in ANCA-associated vasculitis supports B-cell-targeted therapy.

At present, it is believed that rituximab has the same effect as cyclophosphamide are the same. A meta-analysis is made in this paper based on the synthesis of all the studies.

Materials and Methods

We conducted a meta-analysis with the methods specified in the Cochrane Handbook for Systematic Reviews of Intervention [12]. Pubmed, Embase, Cochrane Library, CNKI and Wanfang database were used to retrieve articles with subject words and free words. The deadline was October, 2021. Medical Subject Headings (Mesh) terms or free text are used as follows: “rituximab” or “CD20 Antibody, Rituximab” or “Rituximab CD20 Antibody” or “Mabthera” or “IDEC-C2B8 Antibody” or “IDEC C2B8 Antibody” or “IDEC-C2B8” or “IDEC C2B8” or “GP2013” or “Rituxan” and “ANCA - Associated Vasculitis” or Anti Neutrophil Cytoplasmic Antibody Associated Vasculitis or ANCA-Associated Vasculitis or ANCA Associated Vasculitis or Vasculitis, ANCA-Associated or Pauci-Immune Vasculitis or Pauci Immune Vasculitis or Pauci-Immune Vasculitides or Vasculitides, Pauci-Immune or Vasculitis, Pauci-Immune or ANCA-Associated Vasculitides or ANCA Associated Vasculitides or ANCA-Associated Vasculitide or Vasculitide, ANCA-Associated or Vasculitides, ANCA-Associated and “randomized controlled trial”. With the above retrieval methods, a total of 202 literatures were included, as shown in the Figure 1.