Emerging Therapies in Antineutrophil Cytoplasm Antibody-Associated Vasculitis

Shunsuke Furuta; David Jayne

Disclosures

Curr Opin Rheumatol. 2014;26(1):1-6. 

In This Article

T Cell-Targeted Therapies

Several lines of evidence have shown the importance of T cells in AAV pathogenesis. Expansion of effector memory CD4+ T-helper cells contributes to the local tissue injury and disease progression of AAV, while functional impairment of regulatory T cells in AAV has been reported.[26] Indeed, in the subanalysis of the RITUXVAS trial, T cell tubulitis was an independent predictor for renal outcome assessed by estimated GFR after 12 months.[27] Although B cell-targeted therapy with rituximab is effective in AAV, T cell-targeted therapy as an alternative may be superior in such cases.

Abatacept is a fusion protein of CTLA-4-Ig and the immunoglobulin Fc region, which binds to B7 on antigen professing cells. It inhibits a costimulatory signal of B7-CD28, and consequently inhibits T-cell activation. It is currently approved for rheumatoid arthritis. An open-label pilot study involving relapsing patients with nonsevere GPA demonstrated sustained disease control with abatacept (Vasculitis & ANCA Workshop, April 2013) (ClinicalTrials.gov number; NCT00468208).

Alemtuzumab is an anti-CD52 monoclonal antibody licensed for chronic lymphocytic leukemia and T-cell lymphoma. CD52 is expressed in mature lymphocytes including both T and B cells and macrophages that are depleted by alemtuzumab. Walsh et al.[28] reported alemtuzumab led to sustained treatment free remissions in AAV, but it is strongly immunosuppressive and was associated with severe adverse events in the elderly and those with renal failure. Furthermore, evidence of the efficacy and safety of alemtuzumab in AAV is required before it can be included in treatment options for refractory disease.

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