TO037
CLINICAL PREDICTORS OF RESPONSE TO RITUXIMAB IN ANCA-ASSOCIATED VASCULITIS: A EUROPEAN COHORT

Introduction and Aims: Rituximab (RTX) is a licensed therapy for ANCA vasculitis (AAV). We have explored clinical predictors of response in a large European cohort.

Methods: Patients with relapsing-refractory AAV receiving RTX as induction in 11 European centres were studied. We defined treatment failure (TF) active vasculitis requiring immunosuppressive treatment escalation after RTX. We identified clinical factors predicting TF 6 months after RTX and TF free survival; follow up was censored at retreatment with RTX. B-cell return was a B-cell count ≥0.01x10⁹/l

Results: 322 patients were followed for 16.7 months; aged 54 years (IQR 41-65), 160 (50%) were male, 278 (86%) had granulomatosis with polyangiitis (GPA/Wegeners), 70% had PR3-ANCA, 15% MPO-ANCA and 15% were ANCA negative. TF rate at 6 months was 13% and the median TF free survival was 29.5 months. 20% experienced serious adverse events by 6 months (hospitalisation, 49; intravenous therapies, 20; life threatening disease, 5; cancer in 4). Prednisolone dose and number of immunosuppressive medications reduced from 20mg (IQR 10-37.50) and 2 (IQR 1.75-3) at the time of RTX to 7.5mg (IQR 5-10) and 0 (IQR 0-1) by 6 months (p<0.001). Of baseline characteristics, only kidney involvement was associated with a lower risk of TF at 6 months (OR 0.35, 95%CI 0.12-0.84, p=0.028). Patients with kidney involvement had lower median cyclophosphamide exposure (7g vs 13.5, p<0.001) and a lower proportion of ENT involvement (41%vs69%, p<0.001). 15% of patients had detectable B cells at 6 months and this group was more often ANCA positive at this time (OR 3.18, 95%CI 1.1-10.7, p=0.03), neither factors were associated with risk of TF. IgG and IgM levels reduced 6 months after RTX respectively of a median of -0.45 g/l and -0.2 g/l (p<0.001); factors associated with higher IgG reduction were administration of cyclophosphamide together with RTX (OR 4.5, 95%CI 1.8-11.3), IgG baseline levels (OR 1.4, 95%CI 1.2-1.6), DEI score (OR 1.2, 95%CI 1.1-1.4) and prednisolone dose (OR 1.02, 95%CI 1.01-1.04). Patients with an age at the time of RTX ≤50 years had a shorter TF free survival (23.2 months vs 32.1 months, p=0.01) and the patients that experienced switch of the ANCA from positive to negative by 6 months had a longer TF free survival (39.8 months vs 29.2 months, p=0.01).

Conclusions: In a large European cohort with relapsing-refractory AAV, RTX was an effective treatment. Kidney involvement, age >50 years and switch of the ANCA to negative 6 months after treatment were favourable prognostic factors.