Anticytokine Therapies
Inflammatory cytokines are important components in the disease development of AAV. Among these, TNF-α is associated with disease activity in GPA and TNF-α blockade has abrogated experimental renal vasculitis. Although small studies in patients with refractory disease showed promising results, a randomized, placebo-controlled trial evaluating the efficacy of etanercept, one of the TNF-α inhibitors, in the achievement of sustained remission in GPA patients failed to show efficacy. A glucocorticoid sparing role of TNF-α inhibitors in remission induction was suggested in pilot studies of infliximab and adalimumab but their further development has not been pursued. Consequently, TNF-α inhibitors are not currently recommended in AAV therapy.
Interleukin (IL)-6 is another representative inflammatory cytokine. It was demonstrated that ANCA induced the production of IL-6 by endothelial cells in vitro, and a case report suggested that tocilizumab, anti-IL-6 receptor antibody, was effective for MPA.
Recently, Th17 cells have been considered to play an important role in the disease development of AAV and in early granuloma formation in GPA. IL-23 is a cytokine essential for the proliferation of Th17 cells. Ustekinumab is an anti-IL-12/23p40 monoclonal antibody, and might be effective for AAV as well as other autoimmune disease related to Th17 cells such as psoriasis.