Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

Gulati, Kavita; Edwards, Helena; Prendecki, Maria; Cairns, Thomas; Condon, Marie; Galliford, Jack; Griffith, Megan; Levy, Jeremy; Tam, Frederick W.K.; Tanna, Anisha; Pusey, Charles D.; McAdoo, Stephen P

doi:10.1016/j.kint.2021.08.025

Cited by 42 publications

(21 citation statements)

References 27 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For what is concerning the most critical patients of AAV, i.e., those with eGFR <15 mL/min/1.73 m 2 and >50% crescents in nonsclerotic glomeruli at the renal biopsy, in a singlecenter pilot trial, a combination of RTX, low-dose CYC, and GCs (the so-called intensive B-cell depletion protocol) added to plasma exchange achieved a BVAS = 0 at 6 months in 14 out 15 patients (93%) with recovery of renal function, allowing dialysis discontinuation in 6 out of 10 dialysis-dependent patients [61]. Similar findings were observed in 64 patients (50% dialysis-dependent) having a mean eGFR 9 mL/min/1,73 m 2 treated with a similar regimen [58].…”

Section: The New Challenge Of Anticomplement Treatment Of Aavmentioning

confidence: 52%

“…Prolonged administration of RTX (two more years) further reduced the relapse rate in the MAINRITSAN 3 study [56]. However, induction regimens combining RTX and CYC seem to achieve long-lasting remission without a maintenance regimen, especially in MPO-AAV [57][58][59][60]. Could avacopan have a role as a maintenance regimen?…”

Section: The New Challenge Of Anticomplement Treatment Of Aavmentioning

confidence: 99%

See 1 more Smart Citation

How the Availability of Anti-C5a Agents Could Change the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Roccatello¹,

Fenoglio²,

Oddone³

et al. 2022

Kidney Blood Press Res

View full text Add to dashboard Cite

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a cluster of potentially life-threatening disorders often involving the kidney with a necrotizing crescentic glomerulonephritis with scanty deposition of immunoglobulins and complement. Historically the role of complement has been considered ancillary. Recently, an anti-myeloperoxidase (MPO) AAV model in complement-deficient mice has shown an involvement for the complement cascade in the development of the renal injuries. Further animal studies showing that in contrast to mice deficient for factor B and C5 animals deficient for C4 were susceptible to AAV development by injection of anti-MPO antibodies emphasized the specific involvement of the alternative pathway. Consonantly, the C5a receptor (Cd88) blockade was found to protect mice from MPO AAV. CCX168, i.e., Avacopan, a powerful inhibitor of C5a receptor that can be administered orally, was shown to reduce the pro-inflammatory effects of C5a and abolish the activation of neutrophils, their migration and adherence to endothelium, and the vascular endothelial cell retraction that increases permeability. Summary: Avacopan was found to be safe in healthy volunteers given a wide range of doses in a Phase 1 clinical trial. The Phase 2 trial CLEAR assessed the possibility to decrease dose or entirely replace glucocorticosteroids in the Standard of Care (SoC) therapy of AAV. Avacopan, added to CYC or RTX either in combination with GCs or not, shortened the time to remission in patients with either newly diagnosed or relapsing AAV. The Phase 3 ADVOCATE study compared the ability of an Avacopan-associated regimen to induce and sustain remission in AAV patients vs a conventional GC-associated scheme. Remission at week 26 was observed in 72.3% of patients given Avacopan and in 70.1% of those given prednisone. Sustained remission at week 52 (second primary endpoint) was obtained in 65.7% of patients given Avacopan and in 54.9% receiving prednisone. The Avacopan-associated regimen was non-inferior at week 26, and superior at week 52 in sustaining remission as compared to the GC-based scheme. Key point: The results of the ADVOCATE trial opened new prospects for the treatment of AAV and also other immune-mediated diseases with renal involvement. The possible position of Avacopan in a routinary clinical setting and its possible indications in specific subsets of patients with AAV are extensively discussed.

show abstract

Section: The New Challenge Of Anticomplement Treatment Of Aavmentioning

confidence: 52%

Section: The New Challenge Of Anticomplement Treatment Of Aavmentioning

confidence: 99%

How the Availability of Anti-C5a Agents Could Change the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Roccatello¹,

Fenoglio²,

Oddone³

et al. 2022

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…The differences, however, were marginal and the only statistically significant comparison involved mycophenolate mofetil and methotrexate [93]. A combination of immunosuppressants (rituximab, CYC, GC) was not associated with a higher rate of severe infections in a cohort of patients with life-threatening AAV [94]. However, highdose GC added to rituximab may be related to a greater incidence of severe infections in a randomized clinical trial of patients with AAV but without severe glomerulonephritis or alveolar hemorrhage [95].…”

Section: Immunosuppressive Agents and Infections In Vasculitidesmentioning

confidence: 99%

Overview of infections as an etiologic factor and complication in patients with vasculitides

et al. 2022

View full text Add to dashboard Cite

Vasculitides, a form of inflammatory autoimmune disease targeting the vessels, constitute an entity with significant morbidity and mortality. Infections have long been associated with vasculitides as a result of the incident immunosuppression following treatment induction and maintenance. Several microbial pathogens have been described as etiologic factors of infections in this patient population according to the type of vessels affected. Intense research has also been recently conducted in the interplay between vasculitides and certain viral infections, namely human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. Of note, a plethora of scientific evidence is available regarding the role of infections as triggering factors for vasculitides. Among the main mechanisms implicated in this direction are the activation of B and T cells, the direct endothelial insult, the immune complex-mediated vascular injury, and the cell-mediated, type IV hypersensitivity vessel damage. Therefore, this review aims to summarize all the available evidence concerning this bidirectional interplay between infections and vasculitides.

show abstract

“… 113 Significant differences in outcome were noted in a cohort of patients requiring dialysis at outset and those presenting with serum creatinine >500 μmol/L but not requiring dialysis. 114 As a result, further work to explore the benefit of PLEX in patients with severe kidney involvement or pulmonary haemorrhage is warranted.…”

Section: Managementmentioning

confidence: 99%

ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

Austin¹,

Janagan²,

Wells³

et al. 2022

JIR

View full text Add to dashboard Cite

The ANCA associated vasculitides (AAVs) affect a range of internal organs including ear nose and throat, respiratory tract, kidneys, skin and nervous system. They include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). The AAVs are treated with high dose glucocorticoids, immunosuppressants, and targeted biological medications. Since the 1990s classification criteria for the AAVs have been based on clinical features, laboratory tests and basic imaging; an initiative to update the classification criteria incorporating newer tests, for example, anti-neutrophil cytoplasmic antibodies (ANCA) and novel imaging techniques will be published this year. There is also evidence for classification of patients based on ANCA subtype; those with anti-proteinase 3 antibodies (PR3) or anti-myeloperoxidase antibodies (MPO) have differences in response to treatment and clinical outcomes. An update is described within this review. The pathogenesis of AAV involves necrotizing inflammation of small to medium blood vessels involving multiple immunological pathways. We present an update on emerging evidence related to auto-antibodies, complement and lymphocyte pathways. This review describes emerging treatment regimens, including evidence for plasma exchange in severe disease and the inhibitor of the complement C5a receptor (C5aR) inhibitor, Avacopan. Lastly, patient reported outcomes are key secondary outcomes in randomised controlled trials and increasingly clinical practice, we report development in disease specific and glucocorticoid-specific PROs.

show abstract

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

Cited by 42 publications

References 27 publications

How the Availability of Anti-C5a Agents Could Change the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

How the Availability of Anti-C5a Agents Could Change the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Overview of infections as an etiologic factor and complication in patients with vasculitides

ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

Contact Info

Product

Resources

About