Biosimilars of Rituximab in ANCA-associated Vasculitis Compared to the Originator (BRAVO): a CanVasc Multicentre Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 201
- 试验地点
- 9
- 主要终点
- Proportion of participants with a relapse
研究概览
简要总结
The goal of this multicentre observational study is to compare the safety and effectiveness of rituximab biosimilars to the originator in Canadian patients with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), two main forms of ANCA-associated vasculitis (AAV).
The main questions it aims to answer are:
- Is there a difference in vasculitis control between originator and biosimilar rituximab?
- Is there a difference in adverse effects between originator and biosimilar rituximab?
- In the Canadian healthcare context, are wait times to receive approval (financial coverage) for rituximab shorter for biosimilars compared to originators?
Investigators will perform study assessments (including recording disease activity, damage, and adverse events) at the time of participants' usual clinical care visits, at regular intervals for 2 years after starting rituximab (for induction or maintenance treatment) or switching from an originator to a biosimilar as part of their usual care.
Researchers will compare outcomes among participants who have received rituximab originators (from 2018 onwards) or biosimilars as part of their usual care, to see if there are differences in relapses, remission rates, damage, serious infections, serious adverse events, and treatment approval wait times.
详细描述
Background. Rituximab (RTX), a B-cell depleting therapy, has comparable efficacy to cyclophosphamide for induction of remission in severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and superior efficacy to azathioprine for maintenance of remission (1,2). RTX is now a first-line therapy for remission induction and maintenance of remission in severe GPA and MPA (3).
Biosimilar RTX agents are molecules that are highly similar in structure to the 'originator' RTX that was initially studied and approved for the treatment of AAV. Among patients with rheumatoid arthritis, randomized controlled trials have demonstrated comparable efficacy and safety between originator and RTX biosimilars (4,5). Extension studies found that switching from originator to biosimilar does not alter disease activity, immunogenicity, or safety (6,7). Conversely, data on the outcomes of RTX biosimilars in AAV are limited. A retrospective study from Korea included 26 patients (~80% MPA) who received either Truxima (n=15) or Mabthera/Rituxan (n=11) for second-line induction after failure or intolerance to cyclosphosphamide (CYC) (8). There were no obvious deviations in relapse, mortality, end-stage kidney disease, or cardiovascular outcomes compared to other studies with similar populations. A second study was a retrospective cohort study of 77 patients with GPA in India who received RTX biosimilars not available in Canada (Reditux, Rituxipca, Mabtas) for induction, maintenance, or both (9). Outcomes were comparable to those observed in randomized controlled trials of the originator drug.
Despite this scarce amount of data, many Canadian provincial and private funders are mandating the use of biosimilar agents (e.g. Truxima, Ruxience, Riximyo) for induction and maintenance of GPA and MPA, in place of the originator drug (Rituxan). There is a need for longitudinal prospective studies to determine comparative safety and effectiveness of RTX biosimilar agents in Canadian patients with GPA or MPA.
The COVID-19 pandemic has raised concerns for patients and providers about the safety of immunosuppression with RTX. Cohort studies of patients with rheumatic disease have reported an association between RTX and the risk of severe COVID-19 and death from COVID-19 (10-12). Rituximab may also reduce the immunogenicity, and thus the effectiveness, of COVID-19 vaccination, as has been observed for other vaccines (13).
Objectives. The overarching objective of this study is to compare the real-world safety and effectiveness of originator and biosimilar RTX for the treatment of GPA/MPA.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prospective cohort:
- •Initiated within the last 6 months:
- •RTX biosimilar or originator for induction OR
- •RTX biosimilar or originator for maintenance (with or without prior RTX induction) OR
- •Switched from RTX originator maintenance to biosimilar maintenance (4-12 months between infusions)
- •Historical cohort:
- •Followed in a prospective longitudinal cohort study/registry within the CanVasc network, and initiated the following after January 1, 2018 but >6 months prior to study enrollment
- •RTX biosimilar or originator for induction OR
- •RTX biosimilar or originator for maintenance (with or without RTX induction)
排除标准
- •patients without a diagnosis of GPA or MPA
- •patients who did not/are not receiving RTX induction or maintenance therapy
- •patients who initiated most recent RTX treatment course prior to Jan 1, 2018
- •patients receiving RTX for reasons other than GPA or MPA induction or maintenance (e.g. other concurrent disease)
- •unable to provide informed consent
结局指标
主要结局
Proportion of participants with a relapse
时间窗: 6 months
Relapse will be defined as active disease in any organ system (BVAS v3\>0) after remission had previously been achieved AND need to escalate glucocorticoids (GC) to ≥20 mg/day OR change immunosuppression, including receiving RTX infusion earlier than planned/higher dose than planned The proportion of participants with relapses at 6 months will be compared between groups.
Time to relapse
时间窗: From Month 0 until date of first relapse, assessed up to 24 months
Relapse will be defined as active disease in any organ system (BVAS v3\>0) after remission had previously been achieved AND need to escalate glucocorticoids (GC) to ≥20 mg/day OR change immunosuppression, including receiving RTX infusion earlier than planned/higher dose than planned. Survival analyses will compare time to disease relapse between originator and biosimilar recipients, adjusting for potential confounders
次要结局
- Proportion in clinical remission 6 months post-induction(6 months)
- Time to RTX discontinuation due to treatment failure(From Month 0 until date of first relapse, assessed up to 24 months)
- Proportion with a Serious Adverse Event (SAE)(24 months)
- Change in Vasculitis Damage Index (VDI)(From Baseline (Month 0) to 24 months)
- Proportion with a Relapse(24 months)
- Time to Serious Adverse Event (SAE)(From baseline (Month 0) until date of first SAE, assessed up to 24 months)
- Wait time (days) from RTX application to approval and first infusion(6 months)
- Proportion with a Serious Infection (SI)(24 months)
- Proportion with Major relapse(24 months)
- Proportion needing to discontinue RTX due to treatment failure(24 months)
- Time to major relapse(From Month 0 until date of first major relapse, assessed up to 24 months)
- Proportion of participants with a major relapse(6 months)
- Time to Serious Infection (SI)(From baseline (Month 0) until date of first SI, assessed up to 24 months)
研究者
Arielle Mendel
Assistant Professor, Division of Rheumatology; Clinician Investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre