111. Target-to-B! Prospective immunophenotyping in ANCA vasculitis PROMAVAS study design and interim analysis on clinical outcome

Background: ANCA-associated vasculitis (AAV) is an autoimmune disease characterized by antibodies against myeloperoxidase (MPO) and proteinase-3 (PR3) in most patients. The resulting inflammatory response in the small to medium sized blood vessels can lead to organ damage and subsequently to potential life-threatening disease. Cyclophosphamide (CYC) and rituximab (RTX) are potent drugs for the induction of remission, but relapse rates remain high. The identification and prediction of patients at risk, on the other hand, is very difficult in daily practice. As a part of the Target-to-B consortium, a Dutch national project supporting overarching research in the field of B-cell mediated diseases, we set up a prospective cohort of AAV patients. The main objective for this study is to monitor the immune phenotype over time, before and after start of immunosuppressive therapy, and to integrate and correlate these findings with clinical outcome data. Methods: Patients with a major disease presentation of AAV requiring remission-induction therapy, who are either newly diagnosed or have relapsing disease, are included in the Prospective Maastricht ANCA Vasculitis (PROMAVAS) study. Clinical and routine laboratory parameters, as well as research specimen are collected before and 6 weeks, 3 months, 6 months, and 1 year after therapy. After this, sampling takes place on a yearly basis. Laboratory parameters include renal function, CRP, MPO- or PR3-ANCA and immunoglobulin levels, B- and T-cell subsets, urine spot analysis, and in addition we collect serum, plasma, DNA, RNA, PBMC, urine and, when applicable, tissue samples. Clinical data include organ involvement, therapy, previous disease presentations, and disease duration at baseline and relapse rate, infections, renal function, malignancy, and mortality during follow-up. Results: Since 2019, we have screened 101 patients and included 85 patients. Currently, 56 patients are followed for at least one year, with a median follow-up of 22 months (IQR 16-26). An interim analysis on clinical data in this group of patients has been performed. Of these patients, 27 (48.2%) presented with MPO-ANCA positivity, 28 (50.0%) with PR3-ANCA positivity, and 1 (1.8%) with both. Thirty-eight (67.9%) of the patients had biopsy proven renal involvement, with a baseline median serum creatinine level of 236 µmol/L (IQR 149-307). Baseline characteristics of the total cohort and the patients followed for at least 1 year are depicted in Table 1. In addition to corticosteroids in all patients, 30 (53.6%) patients were treated with RTX (2 x 1000mg) and 5 (8.9%) with a combination of RTX (2 x 1000mg) and CYC IV (2 x 15mg/kg), both followed by RTX maintenance depending on ANCA levels, B cell counts, and clinical symptoSixteen (28,6%) patients were treated with oral CYC for 3-6 months, followed by azathioprine for 2 years. Five patients received a different remission-induction regimen. During follow-up, 6 patients died after a median of 6 months (IQR 1-9), of which 2 died due to a SARS-CoV-2 infection. Twelve patients had a major relapse after a median of 15 months (IQR 12-19). The majority of the patients with disease relapse had renal involvement (73%), was treated with RTX without additional CYC (73%), and had PR3-ANCA positivity (82%). Conclusion: With this ongoing prospective study we were able to set up a large, unique, and well-described cohort of AAV patients that is linked to an extensive biobank. We are planning to perform experiments in cooperation with the consortium on deep immune cell phenotyping in the nearby future. The insights that will be gained will help to better identify active disease, evaluate treatment effects, and predict future relapses. Disclosures: None Table 1. Baseline characteristics of the total AAV cohort and the patients followed for at least 1 year. Total cohort, N = 85 >1 year follow-up, N = 56 Age in years, median (IQR) 66 (57-74) 66 (55-74) Male, n(%) 53 (62.4) 37 (66.1) ANCA type, n(%) MPO PR-3 Double positive 39 (45.9) 44 (51.8) 2 (2.4) 27 (48.2) 28 (50.0) 1 (1.8) Diagnosis, n(%) MPA GPA 25 (29.4) 60 (70.6) 16 (28.6) 40 (71.4) De novo, n(%) 48 (56.5) 27 (48.2) BVAS, median (IQR) 14 (12-18) 15 (12-18) Renal involvement, n(%) 54 (63.5) 38 (67.9