COVID-19 and ANCA-associated vasculitis: recommendations for vaccine preparedness and the use of rituximab.

COVID-19 and ANCA-associated vasculitis - recommendations for vaccine preparedness and the use of rituximab

Should We Still Use Therapeutic Plasma Exchange for Rapidly Progressive Glomerulonephritis in ANCA Associated Vasculitis?

For over thirty-five years, available data suggested that therapeutic plasma exchange (TPE) was a useful treatment for patients with Rapidly Progressive Glomerulonephritis (RPGN) associated with ANCA Associated Vasculitis (AAV) and elevated creatinine levels. The publication of the PEXIVAS study has challenged this conclusion. This perspective will outline the history of this issue and present our assessment of the current status

Plasma exchange in ANCA-associated vasculitis : the pro position

Plasma exchange (PLEX) is capable of removing significant amounts of circulating antibodies. In anti-neutrophil cytoplasmic antibody-associated vasculitis, PLEX was reserved for patients with severe presentation forms such as rapidly progressive glomerulonephritis and pulmonary haemorrhage. The Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial included all comers with a glomerular filtration rate <50 mL/min/1.73 m2 and thus aimed to answer the question of whether PLEX is an option for patients with no relevant kidney function impairment or not. PEXIVAS revealed that after a follow-up of almost 3 years, routine administration of PLEX does not provide an additional benefit to reduce the rate of a composite comprising end-stage kidney disease or death. In the absence of histological parameters, it is tempting to speculate whether PLEX is effective or not in those with a potential for renal recovery. A subset of patients presented with alveolar haemorrhage, and there was a trend towards a better outcome of such cases receiving PLEX. This would be in line with observational studies reporting a recovery of alveolar haemorrhage following extracorporeal treatment. In this PRO part of the debate, we highlight the shortcomings of the PEXIVAS trial and stimulate further research paths, which in our eyes are necessary before abandoning PLEX from the therapeutic armamentarium

Intravenous pulse methylprednisolone for induction of remission in severe ANCA associated Vasculitis: a multi-center retrospective cohort study.

BACKGROUND Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. METHODS We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 μmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. RESULTS Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4-5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94-20.63], p = 0.002), after adjustment for confounding factors. CONCLUSIONS The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes

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 biomarkers, 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

Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis

Background and objectives The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.Design, setting, participants, & measurements Avalidation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.Results The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P < 0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In themeta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, andhigh-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study.Conclusions The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.Development and application of statistical models for medical scientific researc