PREP-ANCA: Randomized Trial of Pre‑emptive Rituximab Versus Clinic‑Biological Surveillance for ANCA Re‑positivation in GPA and MPA Patients in Remission

The primary objective is to determine whether a pre‑emptive rituximab strategy is superior to clinic‑biological surveillance performed every three months in preventing disease reactivation in patients with granulomatosis with polyangiitis and microscopic polyangiitis who have achieved complete remission after an 18‑month rituximab course; remission is defined by a Birmingham Vasculitis Activity Score of 0, a clinically relevant endpoint that reflects sustained disease control and reduced organ damage. Secondary objectives include:

• Comparison of the proportion of participants experiencing minor or major relapse.
• Assessment of treatment tolerance, with emphasis on the incidence of severe infections.
• Comparison of the number of rituximab infusions required during follow‑up.
• Comparison of the cumulative rituximab dose administered.
• Evaluation of sequelae occurring during follow‑up.
• Comparison of health‑related quality of life over the study period.
• Determination of overall mortality.
• Comparison of the cumulative corticosteroid dose between arms.
• Comparison of changes in ANCA levels and CD19 cell counts.

The trial enrolled adult patients (age ≥ 18 years) of both sexes who had a confirmed diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis according to the ACR/EULAR 2022 classification criteria and were in complete remission (BVAS = 0) after a prior 18‑month course of rituximab. Participants were required to have recent ANCA repositivation, be able to give written informed consent, and be affiliated with a social security system. Both male and female subjects, including those classified as vulnerable, were eligible. The sponsor did not provide information on the total number of participants enrolled. No specific lifestyle restrictions or requirements were stipulated in the available data.

The study is a phase IV, randomized, controlled trial evaluating pre‑emptive rituximab versus clinic‑biological surveillance in patients with granulomatosis with polyangiitis or microscopic polyangiitis who are in complete remission and demonstrate ANCA re‑positivation. After an initial screening visit to confirm eligibility, participants are randomized to either a pre‑emptive treatment arm receiving a 500 mg intravenous infusion of rituximab (repeat dose on day 15 if required) or a monitoring arm undergoing clinical and laboratory assessment every three months. Follow‑up visits occur at month 3, 6, 9, 12, 15, 18, 21 and 24, during which ANCA status, B‑cell counts, corticosteroid use, adverse events and disease activity are recorded; the primary efficacy endpoint is survival without relapse, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 throughout the 24‑month observation period. The end‑of‑study visit at month 24 includes final assessments of relapse, quality‑of‑life questionnaires, and safety outcomes. Participant involvement therefore spans approximately 24 months plus the screening period. Early termination may occur if a relapse (BVAS > 0) is observed, if serious adverse events arise, if the participant withdraws consent, or if major protocol deviations are identified.

The investigational product is Truxima 500 mg concentrate for solution for infusion, containing the active substance rituximab. It is supplied as a solution for infusion and administered intravenously at a dose of 500 mg per infusion. The infusion is performed according to the study protocol, with the exact frequency determined by the occurrence of ANCA re‑positivation as defined in the trial criteria.

The comparator arm includes a reference rituximab product, also given intravenously at a dose of 500 mg per administration. This product is provided without a specified pharmaceutical form in the source data and is administered following the same infusion procedures as the investigational product.

Patients in the comparator group receive oral prednisone at a dose of 15 mg daily. The medication is supplied in tablet form and taken by mouth as directed by the protocol.

All study medications are recorded in the case report form at each visit. Intravenous infusions are monitored for adherence by documenting infusion start and end times, volume infused, and any interruptions. Oral prednisone compliance is assessed through pill counts and patient diaries. Any deviations from the prescribed dosing schedule are reported to the study monitor in accordance with the monitoring plan.

Efficacy will be evaluated primarily by the proportion of participants who remain relapse‑free over a 24‑month follow‑up period. Relapse is defined as a Birmingham Vasculitis Activity Score greater than 0, whereas maintenance of remission requires a score of 0.

Secondary efficacy parameters include the number of participants experiencing major or minor relapse, the incidence of adverse and serious adverse events, the total number of rituximab infusions administered, sequelae classified by the VDI, quality‑of‑life outcomes measured with the HAQ and SF‑36 instruments, overall mortality, cumulative corticosteroid dose and duration, and longitudinal changes in ANCA titers and CD19⁺ B‑cell counts together with their correlation to clinical events.

Clinical disease activity will be assessed with the validated BVAS at baseline and at scheduled visits every three months throughout the study. Laboratory measurements of ANCA and CD19⁺ B‑cell counts will be obtained at the same three‑month intervals. Patient‑reported outcome questionnaires (HAQ and SF‑36) will be administered at these visits. Time‑to‑relapse will be analyzed using survival methods, while secondary endpoints will be evaluated with descriptive statistics and appropriate comparative tests to determine differences between the pre‑emptive rituximab strategy and the clinic‑biological monitoring arm.