Induction Therapy Failure in Granulomatosis With Polyangiitis Linked to Disease Characteristics

Granulomatosis manifestations were found to be associated with cyclophosphamide induction failure among patients with GPA.

In granulomatosis with polyangiitis (GPA), induction failure is associated with disease characteristics, according to the results of a study published in Rheumatology.

Researchers aimed to identify predictors of GPA induction therapy failure.

Data for the retrospective nationwide study were collected from the French Vasculitis Study Group (FVSG) network. Patients with GPA with an induction failure between 2006 and 2021 were age-, sex-, and treatment-matched in a 1:3 ratio with patients without induction failure.

Failure was defined as lack of remission at 6 months; remission was defined as Birmingham Vasculitis Activity Score (BVAS) of 0, and salvage therapy was defined as the modification of immunosuppressive agents.

Patients with failure and remission were aged a median of 49) and 44.8 to 49 years; 56.9% and 54.2% to 59.3% were men; 43.1% and 12.5% to 92.6% were newly diagnosed with GPA; and BVASs were 19and 14.5 to 19 points, respectively.

In the induction failure group (n=51), 27 had an inadequate response to intravenous cyclophosphamide (CYC) and 24 to rituximab (RTX). In addition to induction treatments, 32 (64%) patients received intravenous methylprednisolone pulses and 49 (96%) received oral prednisone at a median initial dose of 60 mg/day, with progressive tapering with 50 mg/day at 1 month progressing to 18 mg/day at 5 months.

Overall, this study increases the understanding of induction failure in GPA and some results corroborate findings of previous studies on smaller populations…

Induction failure occurred due to inappropriate response (45%), disease progression (31%), and relapse (26%). Stratified by induction, the most common failure modalities were inappropriate response for CYC (67%) and progression for RTX (50%). The median time to induction failure was 83 days for all patients.

Stratified by type of failure, the time to failure was shorter for patients with progression (median, 32 days) compared with inappropriate response (median, 94 days) or early relapse (median, 144 days) among CYC and RTX recipients (median, 15 vs 90 vs 138 days), respectively.

The best predictor for CYC induction failure was relapsing disease (odds ratio [OR], 8.3; 95% CI, 2.7-27.8). The best predictor for RTX induction failure was cutaneous involvement (OR, 6.5; 95% CI, 1.9-24.7). Stratified by type of failure, kidney involvement (OR, 6.6; 95% CI, 1.6-31.6) and kidney failure (OR, 7.3; 95% CI, 1.4-45.8) predicted disease progression among those receiving RTX.

Salvage therapy of switching from CYC to RTX or RTX to CYC was requested by 57% of participants. The rate of remission after salvage therapy was 69%.

Study findings may have been biased because the definition of induction failure was too broad.

The study authors concluded, “Overall, this study increases the understanding of induction failure in GPA and some results corroborate findings of previous studies on smaller populations…”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.

References:

Sorin B, Iudici M, Guerry M-J, et al. Induction failure in granulomatosis with polyangiitis: a nationwide case-control study of risk factors and outcomes. Rheumatology. Published online February 27. 2023. doi:10.1093/rheumatology/kead098