In patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) who are treated with rituximab, resistance at 3 months of induction therapy has been reported, according to findings from a French multicenter, retrospective study.

The analysis was conducted between 2010 and 2020, with the results published in the Joint Bone Spine.

AAV, which is known to affect mainly the small vessels, includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In individuals with AAV, the kidneys and the upper/lower respiratory tract are the most commonly, severely affected organs, thus threatening patient prognosis. The treatment of patients with AAV involves the induction of remission, followed by maintenance therapy.

The standard induction treatment for individuals with severe GPA and MPA has been a combination of glucocorticoids and cyclophosphamide (CYC). Rituximab has been shown to be noninferior to CYC at 6 months and is now part of the induction regimen in patients with AAV.

The primary endpoint of the current study was the presence of rituximab resistance at 3 months, which was defined as uncontrolled disease (ie, worsening feature on the Birmingham Vasculitis Activity Score/Wegener [BVAS/WG] at 1 month following rituximab induction) or disease flare (ie, increase in BVAS/WG of ≥1 point prior to 3 months of rituximab induction therapy).

The study enrolled 121 participants, with 5 individuals excluded because they did not attain complete remission at 3 months. Thus, 116 individuals were evaluated. Overall, 59% of the participants were males. The median patient age was 56 years (range, 47-66 years). The majority of the patients had relapsing disease (67%) and GPA (65%). The median BVAS/WG was 5 (range, 3-7). 

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Results of the study demonstrated that at month 3, patients with rituximab resistance compared with those without had a significantly higher percentage of localized disease (43% vs 18%, respectively; P <.05) and were less frequently treated with methylprednisolone pulse (21% vs 58%, respectively; P <.01). Among the 14 participants who exhibited rituximab resistance, 7 were treated with additional immunosuppressive therapy.

All of the participants reported being in remission at 6 months. Patients with rituximab resistance at 3 months, when compared with responders, received prophylactic trimethoprim-sulfamethoxazole treatment less often (57% vs 85%, respectively; P <.05). During follow-up, 24 patients died—33% from infections and 50% from SARS-CoV-2 infection.

“The main challenge in treating refractory patients is not only in achieving remission but decreasing the risk for cardiovascular and infectious events,” the researchers explained. “In this context, the identification of the rituximab-resistant patients at month 3 appears important to propose individualized induction treatment using alternatives to the increasing of glucocorticoids in these patients,” they concluded.


Machet T, Quéméneur T, Ledoult E, et al. Rituximab resistance at 3 months of induction therapy in newly diagnosed or relapsing ANCA associated vasculitis: a French multicentre study. Joint Bone Spine. Published online May 23, 2023. doi:10.1016/j.jbspin.2023.105591