Abstract Objective To assess the effects of plasma exchange on important outcomes in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Design Systematic review and meta-analysis of randomised controlled trials. Eligibility criteria Randomised controlled trials investigating effects of plasma exchange in patients with AAV or pauci-immune rapidly progressive glomerulonephritis and at least 12 months’ follow-up. Information sources Prior systematic reviews, updated by searching Medline, Embase, and CENTRAL to July 2020. Risk of bias Reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. Synthesis of results Meta-analyses were conducted using random effects models to calculate risk ratios and 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. Outcomes were assessed after at least12 months of follow-up and included all-cause mortality, end stage kidney disease (ESKD), serious infections, disease relapse, serious adverse events, and quality of life. Results Nine trials including 1060 participants met eligibility criteria. There were no important effects of plasma exchange on all-cause mortality (relative risk 0.90 (95% CI 0.64 to 1.27), moderate certainty). Data from seven trials including 999 participants that reported ESKD demonstrated that plasma exchange reduced the risk of ESKD at 12 months (relative risk 0.62 (0.39 to 0.98), moderate certainty) with no evidence of subgroup effects. Data from four trials including 908 participants showed that plasma exchange increased the risk of serious infections at 12 months (relative risk 1.27 (1.08 to 1.49), moderate certainty). The effects of plasma exchange on other outcomes were uncertain or considered unimportant to patients. Limitations of evidence There is a relative sparsity of events, and treatment effect estimates are therefore imprecise. Subgroup effects at the participant level could not be evaluated. Interpretation For the treatment of AAV, plasma exchange has no important effect on mortality, reduces the 12 month risk of ESKD, but increases the risk of serious infections. Funding No funding was received. Registration This is an update of a previously unregistered systematic review and meta-analysis published in 2014.

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The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis

Background Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4–5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

/pdf/eular-recommendations-for-the-management-of-anca-associated-3o8vpfth.pdf

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence‐based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence‐based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and 166 graded and categorized indications. This includes seven new fact sheets, nine new indications on existing fact sheets, and eight changes in the category for existing indications. The Ninth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue

We sought to elicit patient preferences regarding the use of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and its tradeoffs of risk of kidney failure and risk of serious infection.Patient survey.The online survey was circulated to adults with AAV via kidney and vasculitis networks in Canada, the United Kingdom, and the United States.Respondents reviewed the estimated 1-year risks of kidney failure and serious infection in AAV with and without plasma exchange across 5 serum creatinine categories (150, 250, 350, 450, and 600 μmol/L). For each scenario, participants indicated whether or not they would choose plasma exchange.Responses were assessed with multilevel multivariable logistic regression models to identify predictors of respondent choice regarding treatment with plasma exchange.The 470 respondents from the 13 countries (United States 61.7%, United Kingdom 20.0%, Canada 13.8%, and other countries 4.5%) had a mean age of 58.6 (SD 14.3) years, 70.2% women. Respondents were more likely to choose plasma exchange in scenarios at high risk of kidney failure and serious infection (creatinine level of 350 or 450 μmol/L) compared with lower risk scenarios or the highest risk scenario. However, 145 (30.9%) chose plasma exchange across all scenarios, whereas 80 (17.0%) declined plasma exchange across all scenarios. Respondents from the United Kingdom (OR, 2.61; 95% CI, 1.09-6.22) who received previous dialysis (OR, 2.70; 95% CI, 1.12-6.52) or received previous plasma exchange (OR, 5.62; 95% CI, 2.72-11.61) were more likely to choose plasma exchange, whereas older respondents (OR, 0.98; 95% CI, 0.96-0.99 per 1 year increase) were less likely.Unclear generalizability to non-English-speaking, older, and less health literate adults, possible responder bias, survivor bias, lack of individualized risk assessments for kidney failure, and serious infection.Patients with AAV do not express a consistent choice for plasma exchange, which highlights the need for shared decision making. 

http://www.kidneymedicinejournal.org/article/S259005952200228X/pdf

Plasma Exchange for ANCA-Associated Vasculitis: An International Survey of Patient Preferences

OBJECTIVES
To provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis.


METHODS
PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach.


RESULTS
For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively.


CONCLUSION
This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.

Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis.

Abstract Clinical questions What is the role of plasma exchange and what is the optimal dose of glucocorticoids in the first 6 months of therapy of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)? This guideline was triggered by the publication of a new randomised controlled trial. Current practice Existing guideline recommendations vary regarding the use of plasma exchange in AAV and lack explicit recommendations regarding the tapering regimen of glucocorticoids during induction therapy. Recommendations The guideline panel makes a weak recommendation against plasma exchange in patients with low or low-moderate risk of developing end stage kidney disease (ESKD), and a weak recommendation in favour of plasma exchange in patients with moderate-high or high risk of developing ESKD. For patients with pulmonary haemorrhage without renal involvement, the panel suggests not using plasma exchange (weak recommendation). The panel made a strong recommendation in favour of a reduced dose rather than standard dose regimen of glucocorticoids, which involves a more rapid taper rate and lower cumulative dose during the first six months of therapy. How this guideline was created A guideline panel including patients, a care giver, clinicians, content experts, and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. The recommendations are based on two linked systematic reviews. The panel took an individual patient perspective in the development of recommendations. The evidence The systematic review of plasma exchange identified nine randomised controlled trials (RCTs) that enrolled 1060 patients with AAV. Plasma exchange probably has little or no effect on mortality or disease relapse (moderate and low certainty). Plasma exchange probably reduces the one year risk of ESKD (approximately 0.1% reduction in those with low risk, 2.1% reduction in those with low-moderate risk, 4.6% reduction in those with moderate-high risk, and 16.0% reduction in those with high risk or requiring dialysis) but increases the risk of serious infections (approximately 2.7% increase in those with low risk, 4.9% increase in those with low-moderate risk, 8.5% increase in those with moderate-high risk, to 13.5% in high risk group) at 1 year (moderate to high certainty). The guideline panel agreed that most patients with low or low-moderate risk of developing ESKD would consider the harms to outweigh the benefits, while most of those with moderate-high or high risk would consider the benefits to outweigh the harms. For patients with pulmonary haemorrhage without kidney involvement, based on indirect evidence, plasma exchange may have little or no effect on death (very low certainty) but may have an important increase in serious infections at 1 year (approximately 6.8% increase, low certainty). The systematic review of different dose regimens of glucocorticoids identified two RCTs at low risk of bias with 704 and 140 patients respectively. A reduced dose regimen of glucocorticoid probably reduces the risk of serious infections by approximately 5.9% to 12.8% and probably does not increase the risk of ESKD at the follow-up of 6 months to longer than 1 year (moderate certainty for both outcomes). Understanding the recommendation The recommendations were made with the understanding that patients would place a high value on reduction in ESKD and less value on avoiding serious infections. The panel concluded that most (50-90%) of fully informed patients with AAV and with low or low-moderate risk of developing ESKD with or without pulmonary haemorrhage would decline plasma exchange, whereas most patients with moderate-high or high risk or requiring dialysis with or without pulmonary haemorrhage would choose to receive plasma exchange. The panel also inferred that the majority of fully informed patients with pulmonary haemorrhage without kidney involvement would decline plasma exchange and that all or almost all (≥90%) fully informed patients with AAV would choose a reduced dose regimen of glucocorticoids during the first 6 months of therapy.

https://www.bmj.com/content/bmj/376/bmj-2021-064597.full.pdf

Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline

Breaking bad news is a challenging station in postgraduate exams. Candidates can struggle if they have not practised delivering sensitive information in a professional and empathetic way. Limited experience of using this clinical skill as a junior doctor often compounds candidates' uncertainty in exams. A clear structure is essential for examination success. The most commonly used is the SPIKES framework, the elements of which are Setting, Perception, Invitation, Knowledge, Emotions and Strategy. This is a stepwise approach that allows candidates to break bad news in a structured way. This is beneficial in clinical practice, but is also invaluable in postgraduate exams, which often have prescriptive marking schemes. This article highlights the key topics and pitfalls that candidates may encounter and suggests tips for success in exams.

Mark Farrar

Papers

Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline

Plasma Exchange for ANCA-Associated Vasculitis: An International Survey of Patient Preferences

Breaking bad news: a clinical skill for postgraduate exams.