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. 2023 Nov 2;62(11):3662-3671.
doi: 10.1093/rheumatology/kead098.

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

Boris Sorin  1   2 , Michele Iudici  2   3 , Mary-Jane Guerry  4 , Maxime Samson  5 , Philip Bielefeld  6 , Thibault Maillet  5 , Mathilde Nouvier  7 , Alexandre Karras  8 , Lara Meyer  8 , Christian Lavigne  9 , Alexis Régent  1   2 , Cécile-Audrey Durel  10 , Marc Fabre  11 , Pierre Charles  12 , Quentin Raimbourg  13 , Aurélia Lanteri  14 , Grégory Pugnet  15 , Frédéric Rivière  16 , Marc Pineton de Chambrun  17 , Patrice Cacoub  18 , Guillaume Le Guenno  19 , Pierre Jourdain  20 , Arsène Mekinian  21 , Romain Paule  22 , Jérémie Dion  1   2 , Paul Legendre  1   2   23 , Pascal Cohen  1   2 , Loïc Guillevin  1   2 , Xavier Puéchal  1   2 , Benjamin Terrier  1   2
Affiliations

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

Boris Sorin et al. Rheumatology (Oxford). .

Abstract

Objective: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy.

Methods: 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 three controls matched for age, sex and induction treatment.

Results: 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 more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 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 nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone.

Conclusion: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.

Keywords: ANCA-associated vasculitides; CYC; granulomatosis with polyangiitis; induction failure; rituximab.

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