Expert Consensus Guidelines for Remission Maintenance With Rituximab in ANCA-Associated Vasculitis

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An expert panel of clinicians developed guidelines for the use of rituximab in the maintenance of remission for adult ANCA-associated vasculitis.

Based on emerging evidence and expert consensus, a panel of nephrologists and rheumatologists from the United Kingdom released recommendations for the use of rituximab in the maintenance of remission in adults with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis. This report was published in Rheumatology.

Investigators performed a systematic review of rituximab studies related to systemic vasculitis, granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (EGPA). Recommendations were developed using a modified Delphi exercise, by which the panel identified key issues, devised related questions, elicited expert opinions, and reached consensus. 

Recommendations for Maintenance of Remission in ANCA-Associated Vasculitis

Among patients with new, relapsing, or refractory ANCA-associated vasculitis, the panel recommends the use of rituximab for the maintenance of remission following successful induction of rituximab or cyclophosphamide.

Despite limited evidence related to the EGPA phenotype, the panel advises similar use of rituximab for maintenance therapy as in the GPA and microscopic polyangiitis phenotypes. However, clinicians should be aware that treatment response to rituximab may differ in patients with EGPA and steroidal cessation may be more challenging.

Recommendations for Rituximab Maintenance Regimen

Following successful induction therapy, the panel recommends fixed interval dosing with rituximab (either 500 mg or 1000 mg administered every 6 months for 2 years) over biomarker guided dosing. Among older individuals with comorbidities and postpubertal adolescents, the treatment regimen should be individualized. Patients should be monitored after rituximab withdrawal as risk for relapse may be ongoing.

In the case of refractory disease or relapse occurring while on rituximab maintenance therapy, changes to treatment strategy depend on assessment of disease activity and organ involvement. The panel advises that clinicians refer their patients to specialized treatment centers where reinduction therapy, shortened interval dosing, or addition of concomitant immunosuppression therapies may be considered.

Among patients at high risk for relapse, fixed interval dosing up to 5 years is recommended; an extended treatment regimen should be individualized based on the patient preferences, age, comorbidities, and history with ANCA-associated vasculitis. High-risk patients include those who have experienced previous relapses after rituximab maintenance therapy, those who remain ANCA-positive, and those in whom the consequence of relapse would be organ- or life-threatening.

The panel recommends that biomarkers (ANCA and B-cell counts) alone should not be used to guide treatment decisions in ANCA-associated vasculitis as relapses may occur even in their absence. However, future research should consider the role of biomarkers for measuring disease activity, disease-related damage, and adverse effects of therapy.

Recommendations for Concomitant Therapy


Among patients who already receive disease-modifying antirheumatic drugs (DMARDs) — including azathioprine, methotrexate, or mycophenolate — the panel recommends the withdrawal of existing DMARDs when commencing rituximab maintenance therapy. Although concomitant therapy may be efficacious in this setting, the potential for adverse effects is increased.


After rituximab induction therapy, shorter glucocorticoid tapering strategies are recommended, which should aim for complete glucocorticoid cessation in the first 6 to 12 months. In practice, patients with EGPA face greater challenges with steroidal withdrawal and may experience incomplete control of symptoms.

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Recommendations for Prophylaxis

For patients receiving rituximab maintenance therapy for ANCA-associated vasculitis, Pneumocystis jirovecii prophylaxis is suggested for at least 6 months from when induction therapy is commenced; among high-risk patients, the duration of prophylaxis should be extended and recommencement should be considered when a local cluster of P jirovecii is identified.

Influenza and pneumococcal vaccinations are recommended for all patients. To maximize the effect of these vaccinations, they should ideally be provided 1 month before rituximab infusion; live vaccinations should be avoided.

Recommendations for Adverse Effects


Hypogammaglobulinemia has been consistently observed among patient cohorts receiving rituximab. Therefore, the panel recommends monitoring immunoglobulin levels in all patients receiving rituximab maintenance therapy. If recurrent or atypical infections occur, and if immunoglobulin G levels fall below 3 g/L (or the age-adjusted norm), further clinical investigation is recommended.

Among patients with hypogammaglobulinemia, and in whom a clinically important response to rituximab is expected, parallel administration of rituximab and immunoglobulin replacement therapy may be considered in conjunction with clinical immunology services.

Late-onset neutropenia

Late-onset neutropenia has been identified in patients receiving rituximab maintenance therapy; although the condition is often asymptomatic and typically short-lived, clinicians and patients should practice greater vigilance in the absence of routine testing. However, among patients being treated for autoimmune disease, including ANCA-associated vasculitis, a history of uncomplicated late-onset neutropenia should not limit repeat rituximab administration.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Tieu J, Smith R, Basu N, et al. Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines [published online February 24, 2020]. Rheumatol. doi:10.1093/rheumatology/kez640