New Therapeutic Targets in Antineutrophil Cytoplasm Antibody–Associated Vasculitis

Abstract

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare systemic autoimmune disease that is characterized by necrotizing inflammation of predominantly the small blood vessels and the presence of circulating ANCAs directed against myeloperoxidase or proteinase 3. Current treatment strategies for severe disease, supported by the findings of several well-coordinated randomized controlled trials, aim to induce remission with high-dose glucocorticoids and either rituximab or cyclophosphamide, followed by relapse prevention with a period of sustained low-dose treatment. This approach has dramatically improved outcomes in AAV; however, a significant proportion of patients develop serious treatment-related side effects or experience relapse. Recent advances in our understanding of the pathogenesis of AAV have led to the identification of novel therapeutic targets that may address these problems, including strategies directed at the aberrant adaptive autoimmune response (B and T cell-directed treatments) and those targeting innate immune elements (complement, monocytes, and neutrophils). It is anticipated that these novel treatments, used alone or in combination, will lead to more effective and less toxic treatment regimens for patients with AAV.

ANCA-Associated Vasculitic Neuropathies: A Review

“…The efficacy of anti-IL-5 therapy (i.e., mepolizumab) in suppressing the activation of eosinophils has been demonstrated in patients with refractory or relapsing EGPA [ 63 ]. Several other new agents, including avacopan, vilobelimab, and abatacept, are under development for the treatment of ANCA-associated vasculitis [ 67 , 69 ].…”

“…IFX-1, now called vilobelimab [ 68 ], is a chimeric monoclonal IgG4 antibody against the soluble form of C5a and is being considered as another agent that can inhibit complement activation in patients with ANCA-associated vasculitis. Two phase 2 trials for MPA and GPA are currently in progress (NCT03712345 and NCT03895801) [ 69 ]. Abatacept is a fusion protein of the Fc region of IgG1 and the extracellular domain of cytotoxic T lymphocyte antigen 4.…”

“…An open-label study demonstrated efficacy of abatacept in terms of the frequency of disease remission and prednisone discontinuation in patients with non-severe relapsing GPA [ 71 ]. At present, a phase 3 trial involving patients with non-severe relapsing GPA is ongoing (NCT02108860) [ 69 ].…”

Diagnostic and Therapeutic Approach in ANCA-Associated Glomerulonephritis: A Review on Management Strategies

“…A randomized study, Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE), studied alemtuzumab, a monoclonal antibody against the CD52 on T-cells, targeting them to destruction (190). Although the majority of patients reached remission at 6 months, adverse effects were more common than in standard therapies.…”

Immunoregulatory therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: Low-dose Interleukin-2 therapy increases the reduced Treg cells

“…Recent years, it has been a rising area to study the role of T lymphocytes in AAV. T cells play an important regulatory role in helping B cells to synthesize higha nity antibodies to exert humoral immune response, and the insu cient regulation of T cells can lead to the de ciency of adaptive immune and promote the autoimmune in ammatory response [9,10]. And in animal models, T cells were observed to in ltrate into kidney and other tissues in patients with AAV [11].Thus, T cells may be involved in the development of AAV.…”