What is the role of rituximab in the treatment of granulomatosis with polyangiitis (GPA)?

Updated: Aug 31, 2021
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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Rituximab combined with high-dose glucocorticoids represents an alternative to cyclophosphamide for induction of remission in GPA; it is the first treatment ever approved by the FDA for AAV. [65]

The evidence for this approval came from the Stone et al's RAVE (Rituximab in Antineutrophil Cytoplasmic Antibody ̶ Associated Vasculitis) trial. [19] Rituximab is a chimeric monoclonal anti-CD20 IgG1 antibody that induces apoptosis of B cells, with the exception of plasma cells and pre-B cells. Infusion of rituximab typically causes a 6-month depletion of circulating B cells and therefore may decrease the production of autoantibodies such as ANCAs.

The RAVE trial, which showed the noninferiority of rituximab compared with the cyclophosphamide control group, suggested that rituximab may be better for induction of relapsing disease. There were no significant differences between the treatment groups in the number or severity of adverse events.

The RITUXVAS trial, by The European Vasculitis Study Group (EUVAS), examined the use of rituximab in severe GPA with renal involvement in older patients and found rituximab was not superior to cyclophosphamide and was associated with a similar number of adverse events, although the rituximab group also received cyclophosphamide. [20] Both studies confirmed the efficacy and superiority of rituximab over cyclophosphamide in reducing ANCA positivity. [66]

Further studies may address whether rituximab is effective for limited disease, which is typically associated with more granulomatous features than vasculitic ones. Rituximab is typically thought to be more effective in the vasculitic phase rather than the granulomatous phase, but small studies have shown good results even in limited disease. [67, 68]

Adverse effects associated with rituximab include infusion reactions, mucocutaneous reactions, increased risk of infections (to include opportunistic infections such as progressive multifocal leukoencephalopathy), cytopenias, and malignancy. In rheumatoid arthritis patients, hypogammaglobulinemia before rituximab seemed to be more closely associated with risk of infection than during or after rituximab. [70] Whether rituximab-associated hypogammaglobulinemia is associated with risk of infection in AAV remains to be determined, although a retrospective study did not show an association. [71] Late-onset neutropenia has also been associated with rituximab in GPA; appropriate laboratory monitoring should be considered. [72]

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