Comparison of a Strategy Based on Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment in Cases of ANCA Reappearance in Granulomatosis With Polyangiitis and Microscopic Polyangiitis.

Официальное название

Comparison of Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment for ANCA Repositivation in Granulomatosis With Polyangiitis and Microscopic Polyangiitis: a Prospective, Multicenter, Randomized Controlled Study.

Обзор

The PREP-ANCA study seeks to establish a more personalized treatment strategy for ANCA-associated vasculitides by assessing the efficacy of pre-emptive rituximab administration upon ANCA repositivity in preventing relapses in granulomatosis with polyangiitis and microscopic polyangiitis.

Подробное описание

Treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) is currently based on an induction phase aimed at achieving remission, followed by a maintenance phase to prevent relapse. Rituximab is considered a cornerstone of maintenance therapy, typically administered for a minimum of 18 months. However, the extension of rituximab treatment beyond this period remains debated, primarily due to the increased risk of infections associated with prolonged immunosuppression.

The use of biomarkers to guide treatment duration-extending therapy only in patients at high risk of relapse-represents a promising step toward personalized management. Among the potential biomarkers, ANCA (anti-neutrophil cytoplasmic antibodies) have emerged as a particularly attractive candidate, having been identified as an early marker of relapse. Early studies on pre-emptive immunosuppressive strategies have suggested that timely intervention could reduce relapse rates; however, none of these studies were conducted in the rituximab era. As a result, in the absence of a dedicated prospective randomized trial, current recommendations advise close monitoring in the event of isolated ANCA repositivity in patients who remain in clinical remission.

The objective of this study is to determine whether pre-emptive rituximab administration upon ANCA repositivity is superior to current standard care in reducing the risk of relapse.

Вмешательства

• Препарат Rituximab
  500 mg IV every 6 months for a total duration of 18 months depending on ANCA positivity.

Первичные конечные точки

• Survival without relapse in each arm at 24 months. (relapse defined by The Birmingham Vasculitis Activity Score (BVAS) score > 0) [Срок оценки: 24 months.]

Вторичные конечные точки (10)

• Number of participants with a major or a minor relapse during the study. [Срок оценки: 48 months]
• Number of adverse events [Срок оценки: 48 months]
• Number of serious adverse events such as potentially fatal, requiring hospitalisation, causing significant disability or resulting in death [Срок оценки: 48 months]
• Numbers of rituximab perfusions performed in each arms. [Срок оценки: 48 months]
• The index of damage caused by vasculitis according to the Vasculitis Damage Index (VDI)classification during follow-up [Срок оценки: 48 months]
• Quality of life according to Health Assessment Questionnaire (HAQ ) classifications during follow-up [Срок оценки: 48 months]
• Quality of life according to SF-36 classifications during follow-up [Срок оценки: 48 months]
• Mortality in each arm [Срок оценки: 48 months]
• Cumulative dose and duration of corticosteroid treatment in each arm [Срок оценки: 48 months]
• Evolution of ANCA levels and CD19+ B-lymphocyte in each study arm and their correlation with clinical events [Срок оценки: 48 months]

Критерии участия

Критерии включения

• Adult patients aged ≥ 18 years
• Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria
• Maintenance treatment with rituximab for at least 18 months, administered as follows: a 500 mg infusion on day 1 (with an optional repeat dose on day 15), followed by 500 mg infusions every 6 months for a total of 4 to 5 doses
• Patient in complete remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 at the time of randomization
• ANCA repositivity (confirmed by antigen-specific testing) within the 3 months prior to randomization
• Ability to provide written informed consent prior to participation
• Affiliation to a national health insurance or social security scheme

Критерии исключения

• Diagnosis of any vasculitis other than GPA or MPA
• Active disease relapse, defined as BVAS > 0
• Acute active infection requiring hospitalization or intravenous anti-infective therapy within 4 weeks prior to screening, or oral anti-infective treatment within 2 weeks prior to screening
• History of deep tissue infections (e.g., fasciitis, abscess, osteomyelitis, septic arthritis) within 12 months prior to inclusion
• History of severe, chronic, or recurrent infections, or any underlying condition predisposing the patient to serious infections
• Administration of a live vaccine within 4 weeks prior to study inclusion
• Active malignancy or history of hematologic malignancy within the past 5 years, except for localized prostate cancer or basal cell carcinoma of the skin
• Presence of systemic diseases for which the study treatments may have unpredictable or inappropriate consequences
• History of severe allergic or anaphylactic reactions, or known hypersensitivity to humanized or murine monoclonal antibodies and/or corticosteroids
• Known hypersensitivity to any monoclonal antibody or biologic agent
• Patients previously deemed non-responders or failures to rituximab therapy
• Suspicion of poor adherence to treatment or anticipated inability or refusal to comply with the required follow-up visits and procedures
• Inability or refusal to provide written informed consent Pregnant or breastfeeding women. Women of childbearing potential must use effective contraception during the study and for 6 months after the last infusion. Breastfeeding is contraindicated during treatment and for 6 months following the final rituximab dose.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Hôpital Cochin — Paris

Идентификаторы

NCT: NCT07451847 · APHP240796 · 2025-522049-23-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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