Progress in treatment of ANCA-associated vasculitis

Smith, Rona; Jones, Rachel; Jayne, David

doi:10.1186/ar3797

Cited by 62 publications

(24 citation statements)

References 96 publications

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“…Consistent with this, after a single dose of RTX to treat autoimmunity, disease flare and autoantibody production are common after repopulation of the B-cell pool. 42,62,63 Together, our results suggest that additional treatment targeting Tfh may be required to reduce relapse risk following RTX treatment of autoimmune disease or in the setting of antibody incompatible transplantation. For personal use only.…”

Section: Cd4mentioning

confidence: 67%

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

Wallin

Jolly

Suchánek

et al. 2014

Blood

106

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The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. In this study, we demonstrate that RTX treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of Tfh into account. (Blood. 2014;124(17):2666-2674

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Section: Cd4mentioning

confidence: 67%

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

Wallin

Jolly

Suchánek

et al. 2014

Blood

106

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“…Besides potent therapies used for more than 50 years to induce remission such as cyclophosphamide, others (biologic agents) have been more recently found to be promising or even (for rituximab) as effective as and possibly less toxic than cyclophosphamide, at least for the risks of infertility and late cancers. However, a few patients still experience refractory disease and/ or unrelenting relapses, which underscores the continuing need for newer and more effective therapies (67).…”

Section: Treatmentmentioning

confidence: 99%

Updates in ANCA-associated vasculitis

2016

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Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis, granulomatosis with polyangiitis (Wegener's granulomatosis), microscopic polyangiitis, Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis), cyclophosphamide, rituximab IntroductionAntineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA; al...

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“…Immunosuppressive therapy can result in remission; however, most patients relapse, which results in additional injury (4). Furthermore, chronic immunosuppression leads to additional toxicity.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Pendergraft

Cortazar

Wenger³

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission.Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined.Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase-ANCA) treated from Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted.

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Progress in treatment of ANCA-associated vasculitis

Cited by 62 publications

References 96 publications

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

Updates in ANCA-associated vasculitis

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

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