Induction failure in granulomatosis with polyangiitis: a nationwide case-control study of risk factors and outcomes.

Abstract

To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to 3 controls matched for age, sex and induction treatment. We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure had more frequently PR3-ANCA (93% versus 70%, p= 0.02), relapsing disease (41% versus 7%, p< 0.001) and orbital mass (15% versus 0%, p< 0.01) compared with controls. Patients with disease progression despite RTX induction therapy had more frequently renal involvement (67% versus 25%, p= 0.02) with renal failure (serum creatinine >100 µmol/l in 42% versus 8%, p= 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in 9 (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in 4 (100%) who received ivCYC (with or without immunomodulatory therapy), but only in 3 (50%) after adding immunomodulatory therapy alone. In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.