Evaluation of Rituximab Discontinuation Versus Maintenance Therapy in ANCA-Associated Vasculitis Patients in Stable Remission: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **relapse rate** after discontinuation of rituximab compared with rituximab maintenance in patients with ANCA-associated vasculitis (AAV) who are in stable remission. This is clinically relevant as it aims to determine the efficacy of rituximab discontinuation in maintaining remission, potentially impacting long-term treatment strategies for AAV.

Secondary objectives include:

• Monitoring and investigating relapses, both minor and major, according to rate, time, and proportions.
• Evaluating whether the burden of treatment-related side effects, including infections, is reduced in the discontinuation arm compared to the treatment maintenance arm.
• Assessing adverse event rates.
• Determining if quality of life (QOL) is improved in the discontinuation arm compared to the continuation group.
• Exploring and identifying more reliable and predictive biomarkers for relapse risk in AAV patients in stable remission.
• Investigating health economics by comparing previously used and validated QOL measures in AAV randomized controlled trials, as well as Quality-adjusted Life Years (QALY) by assessing treatment costs and complications/adverse events.

The clinical trial involves a total of **10 participants** diagnosed with **ANCA-associated vasculitis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on their stable remission status, having maintained a **Birmingham Vasculitis Activity Score (BVAS)** of 0 for the last 24 months, and having received a minimum of 24 months of rituximab maintenance therapy, with the last dose administered at least 6 months prior to screening. The trial does not include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified, but females of childbearing potential are required to adhere to adequate contraception methods and must have a negative pregnancy test at the screening visit. The selection criteria ensure that participants have a history of PR3/MPO-ANCA positivity by ELISA and meet the definitions of granulomatosis with polyangiitis or microscopic polyangiitis as per the Chapel Hill Consensus Conference.

The clinical trial is designed to evaluate the **relapse rate** after discontinuation of **rituximab** compared to rituximab maintenance in patients with **ANCA-associated vasculitis** (AAV) who are in stable remission. This study is a randomized, non-blinded, controlled trial. The trial is expected to commence recruitment on August 1, 2024, and conclude by December 31, 2029. Participants will be involved in the study for a maximum treatment period of 36 months. The trial will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. The screening visit will confirm eligibility based on criteria such as a stable remission for the last 24 months and prior rituximab maintenance therapy. Follow-up visits will monitor the primary endpoint, which is the disease relapse rate from randomization to relapse, and secondary endpoints, including time to relapse, maintenance of remission, serological response, and kidney function. The end-of-study visit will assess the overall outcomes and any adverse events. Participants may be withdrawn from the study if they experience significant adverse events or if they no longer meet the inclusion criteria. The trial will adhere to ethical standards, ensuring informed consent is obtained from all participants. The study aims to provide valuable insights into the management of AAV, potentially influencing future treatment protocols.

The clinical trial involves the use of **Rituximab**, an experimental medication, to evaluate its effects in patients with ANCA-associated vasculitis. **Rituximab** is administered in the form of an intravenous drip, with a pharmaceutical form designated as PHF00230MIG. The maximum daily dose of **Rituximab** is 500 mg, and the total maximum dose over the treatment period is 3000 mg. The treatment period is set to a maximum of 36 months. The administration of **Rituximab** is conducted under controlled conditions to ensure participant safety and adherence to the dosing schedule.

In this study, **Rituximab** is compared against a maintenance regimen to assess the relapse rate in patients who have achieved stable remission. The trial does not involve any additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the treatment's efficacy and safety. The trial is designed to provide valuable insights into the management of ANCA-associated vasculitis, focusing on the potential benefits of discontinuing **Rituximab** compared to its maintenance.

Efficacy in the clinical trial titled "Discontinuation of rituximab compared with rituximab maintenance in ANCA-associated vasculitis – a randomized non-blinded controlled trial (DISRITUX)" will be assessed using both primary and secondary endpoints. The primary endpoint is the **disease relapse rate**, measured from randomization to relapse. Secondary endpoints include the time to relapse, the proportion of patients maintaining remission at 24 and 36 months, serological response (ANCA positivity vs. negativity), and loss of kidney function assessed by the eGFR slope at fixed points of 12, 24, and 36 months. Additional secondary endpoints involve the start of kidney replacement therapy, duration and doses of rituximab treatment prior to randomization, duration of glucocorticoid exposure, cumulative glucocorticoid exposure, and cumulative accrual of damage measured by the Vasculitis Damage Index (VDI) scale. Health-related quality of life measurements, serious adverse event rates, frequency of adverse events of special interest, and health economics will also be evaluated.