B cell therapy in ANCA-associated vasculitis: current and emerging treatment options

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an organ-threatening and life-threatening multi-system autoimmune disease in which B cell-derived ANCAs cause neutrophil activation and endothelial damage, strongly implicating these autoantibodies in the pathogenesis of AAV. B cell depletion with rituximab combined with glucocorticoids is associated with a reduction in ANCA concentrations and with clinical remission in the majority of patients with AAV. However, the safety profile of rituximab is no better than that of conventional therapy with cyclophosphamide, and long-term glucocorticoid treatment is needed to achieve and maintain disease-free remission. A need for new therapies exists to reduce the time to remission, to spare the use of glucocorticoids and to promote long-lasting remission without the risk of relapse. Over the past 20 years, there has been great interest in therapeutically targeting B cell cytokines, such as B cell-activating factor (BAFF), in many autoimmune disease settings. Dual B cell-targeted immunotherapy that combines B cell depletion and BAFF blockade could potentially be more efficacious than targeting either mechanism alone. In this Review, the theoretical background for use of this combination approach in AAV is presented and discussed.

Prospects for Anti-B-Cell Therapy in Immuno-Inflammatory Rheumatic Diseases

“…За последние 10 лет было проведено несколько рандомизированных контролируемых исследований (РКИ; табл. 3) и открытых клинических исследований, свидетельствующих об эффективности РТМ в качестве компонента индукционной и/или поддерживающей терапии у пациентов с недостаточной эффективностью ГК и иммуносупрессивных препаратов (в первую очередь ЦФ) у пациентов с АНЦА-СВ [47].…”

Is There a Future for Anti-CD38 Antibody Therapy in Systemic Autoimmune Diseases?

“…However, long-term glucocorticoid treatment is often needed to maintain remission and prevent disease flares. Therefore, to avoid excessive exposure to glucocorticoids and, more importantly, to promote a long-lasting remission of the disease, there is a need for alternative effective treatment options [6].…”

“…Indeed, B cell depletion with the anti-CD20 antibody rituximab has demonstrated to provide beneficial effects in several autoimmune disorders [2][3][4][5]. Rituximab is currently approved for ANCA-associated vasculitis, based on the results of two randomized controlled trials (RCTs) that showed its efficacy in inducing disease remission [6]. Conversely, although commonly used off-label, in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), the use of rituximab is not supported by solid evidence deriving from RCTs, but mostly derived from observational studies [7][8][9].…”

Rituximab and other anti-B-cell agents in immune-mediated inflammatory rheumatic diseases

“…Заболевания Показания РА [14,15] АНЦА-СВ [16,17] СКВ [18][19][20] СШ [21,22] ИВМ [23,24] Возможно назначение в качестве первого ГИБП у высоко-серопозитивных по АЦЦП и IgM РФ Другие показания для назначения в качестве первого ГИБП ционной и/или поддерживающей терапии у пациентов с АНЦА-СВ и недостаточной эффективностью ГК и иммуносупрессивных препаратов, в первую очередь циклофосфамида (ЦФ) [31,32]. В многоцентровое рандомизированное контролируемое исследование RAVE были включены пациенты с рецидивирующим или впервые диагностированным АНЦА-СВ [33].…”