Management of Primary Small-Vessel Vasculitis

Crystal E. Nwannunu, BS; Radhika Shah, BS, MS; Allison L. Limmer, BS, BA; Ravi R. Patel, MD; Uyen Ngoc Mui, MD; Stephen K. Tyring, MD


Skin Therapy Letter. 2020;25(3):5-8. 

In This Article

Future Aims in Management

In the setting of small-vessel vasculitis, future management through a biological approach would potentially be the most beneficial, since pathology of the systemic vasculitides, especially ANCA-associated, is better understood.24 The success of nonselective B-cell depletion using rituximab has paved the way for the next generation of targeted therapies focusing on innate and adaptive immunity. Researchers have noted that B-cellactivating factor (BAFF) is highly involved in stimulating B-cell proliferation and promoting immature B-cell survival. Increased BAFF levels lead to increased production of autoantibodies and is seen in patients with GPA. The ANCA-stimulated neutrophils observed in this disease release BAFF to promote B-cell survival, and because studies have shown increased BAFF after B-cell depletion with rituximab in ANCA-associated vasculitis models, it has been proposed that BAFF may have a key role in promoting autoreactive B-cell survival, facilitating relapse and chronicity of disease. Belimumab, a monoclonal antibody against BAFF in the treatment of systemic lupus erythematosus, has been investigated in a phase III trial to evaluate its efficacy and safety in combination with azathioprine for GPA and MPA maintenance of remission.[25]

In addition, abnormal T-cell activation may also have a role in the pathogenicity of AAV. A study evaluating abatacept, a fusion protein that blocks the T-cell activation co-stimulatory signal, demonstrated disease improvement in 90% of the study population. A phase III trial (NCT02108860) evaluating abatacept in the setting of relapsing, non-severe AAV is ongoing. Component C5a of the complement system has also been implicated in the pathogenesis of AAV. C5a serves as a priming agent for neutrophils, resulting in an increased surface expression of PR3 and MPO. Their interaction with ANCA leads to an amplification loop of ANCA-mediated neutrophil activation, further propagating disease. CCX168 (avacopan) is an orally administered inhibitor of the C5a receptor with phase II data reporting complete remission in a majority of patients receiving a combination of cyclophosphamide or rituximab and CCX168 versus placebo. Although the data is promising, further research is needed.[25]

Finally, it has been shown that inflammatory cytokines may also play an important role in AAV pathogenicity. In patients with active AAV, serum and histopathologic sample levels of IL-6 are increased and appear to be associated with patients who frequently relapse and suffer more severe organ damage. A few case reports have shown that an IL-6 blockade with tocilizumab is successful but requires further evaluation. Along with IL-6, IL-17 and IL-23 may also be involved in more active disease. For this reason, additional research regarding targeted antiinflammatory cytokine therapies is key.[25,26]