Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines—Executive summary

[This is the executive summary of Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines: full guideline, doi: 10.1093/rheumatology/kez640

Interventions for renal vasculitis in adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults.</p> <p>Methods</p> <p>We searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes.</p> <p>Results</p> <p>Twenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegener's granulomatosis.</p> <p>Conclusions</p> <p>Plasma exchange is effective in patients with severe ARF secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil are also effective. Azathioprine, methotrexate and leflunomide are effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.</p

The Sound of Interconnectivity; The European Vasculitis Society 2022 Report

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer -term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among bio-markers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients