Summary

Relaspes are frequent in ANCA-associated vasculitis. Strategies to individualize treatment to prevent relapses while not putting patients at unnecessary risk for infections or adverse events of treatments is an unmet need. In this study, researchers compared two strategies to prevent long-term relapse in patients with ANCA-associated vasculitis. Both strategies used rituximab, one of the standard drugs used to induce and maintain remission. Rituximab acts through depletion of the B cells in the peripheral blood, which also reduces the ANCA autoantibody levels. B cell Depletion typically lasts from  6-18 months after a medication that suppresses the immune system. In previous studies, relapse risk was very low, when patients had no detectable B cells and negative ANCAs. Whether increased ANCA indicates a future disease flare is debated.

In this study, 115 patients who had been in remission for at least two years were divided into two groups. The B-cell group received rituximab when their B-cells started reappearing in their blood, and the ANCA group received rituximab when their ANCA levels significantly increased. Patients were evaluated every three months, and the primary outcome was the occurrence of relapse. The key results of the study were that in the B-cell group, only 4.1% of patients experienced a relapse, compared to 20.5% in the ANCA group. This indicates the B-cell strategy was more effective. Patients in the B-cell group received more rituximab infusions on average (3.6 vs. 0.5 infusions). Both groups had similar rates of serious adverse events, but COVID-19-related complications were slightly higher in the B-cell group. The data suggests that dosing rituximab dependent on the ANCA level may insufficiently prevent relapse. Potentially because other immune reactions occurring before the rise of the ANCA cause the relapse.

In conclusion, a strategy of dosing rituximab based on B-cell levels provides better protection against relapses but requires more infusions and may slightly increase the risk of infection-related complications, such as COVID-19.

Relevance of Results and Implications for Patients with ANCA Vasculitis

Patients in remission from ANCA vasculitis could benefit from the B-cell-based approach due to its significantly lower relapse rates. However, this strategy results in longer/more profound B cell depletion and may need extra monitoring, especially during infectious disease outbreaks. The choice of the treatment strategy may thus also depend on individual risk factors, such as susceptibility to infections and tolerance to rituximab.

References:

[1] Zonozi R et al. Ann Rheum Dis. 2024 Feb 15;83(3):351-359. PMID: 38123922; DOI: 10.1136/ard-2023-224489

Composed by

Dr. med. Christoph Berger
Leitender Arzt
Medizinische Poliklinik
Universitäres Zentrum für Immunologie, Universitätsspital Basel