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Practice Rapid Recommendations

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

BMJ 2022; 376 doi: https://doi.org/10.1136/bmj-2021-064597 (Published 25 February 2022) Cite this as: BMJ 2022;376:e064597
Visual summary of recommendation
Population This recommendation applies only to people with these characteristics: Patients with ANCA associated vasculitis (AAV) ANCA = Antineutrophil cytoplasmic antibody Risk group for end stage kidney disease (ESKD) Baseline serum creatinine level Baseline risk of developing ESKD at 1 year LOW Low to moderate Moderateto high High ≤ 200 µmol/L >200-300 µmol/L >300-500 µmol/L > 500 µmol/L ≤ 2.5% >2.5-7.5% >7.5-25.0% >25.0% Recommendation 3 Recommendation 4 Patients with pulmonary haemorrhage without kidney involvement All patients Requires dialysis Recommendation 1 Recommendation 2
Interventions compared or Plasma exchange added to standard care Standard care alone Recommendations 1-3 or Reduced dose regimenof glucocorticoids Standard dose regimen of glucocorticoids Recommendation 4
Recommendations 1 and 2
Standard carePlasma exchangeorPatients with low orlow-moderate risk ofdeveloping ESKDWe suggest immunosuppression alone without plasmaexchangeStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Rationale

The panel made this recommendation on the basis that for the majorityof patients, moderate to high certainty evidence of a reduction inESKD (0.1% to 2.1% reduction) in patients with low or low-moderaterisk of ESKD does not counterbalance the increase in seriousinfections (2.7% to 4.9% increase) over a timeline of 1 year.
Standard carePlasma exchangeorPatients with moderate-high orhigh risk of developing ESKDor requiring dialysisWe suggest plasma exchange plus immunosuppressionrather than immunosuppression aloneStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Rationale

The panel made this recommendation on the basis of moderate to highcertainty evidence of an important reduction in ESKD (4.6% to 16.0%reduction) and an important increase in serious infections (8.5% to13.5% increase) in patients with moderate-high to high risk of ESKD orrequiring dialysis. The panel considered patients would generallyplace a higher value on avoiding ESKD, and less value on avoiding riskof serious infections.

Evidence profile

Favours standard careFavours plasma exchangeNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
At 1 yearEvents per 1000 peopleEvidence quality

Death from any causeNo important difference116108ModerateMore

Based on data from 967 patients in 6 studiesPlasma exchange probably has little orno effect on death at 1 yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
After more than 1 yearEvents per 1000 peopleEvidence quality

Death from any causeNo important difference222209ModerateMore

Based on data from 1028 patients in 8 studiesPlasma exchange probably has little orno effect on death from any cause aftermore than 1 yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

End stage kidney disease53 fewer281228ModerateMore

Based on data from 996 patients in 7 studiesPlasma exchange probably reducesincidence of end stage kidney diseaseafter more than 1 yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Serious infections50 fewer384434ModerateMore

Based on data from 957 patients in 6 studiesPlasma exchange probably increasesserious infections after more than 1yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Vasculitis relapse21 fewer263242LowMore

Based on data from 202 patients in 3 studiesPlasma exchange may reduce relapse aftermore than 1 yearLowGRADE rating,because of:Risk of biasNo serious concernsImprecisionVery seriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
End stage kidney disease
At 1 yearEvents per 1000 peopleEvidence quality

Low ESKD riskNo important difference21HighMore

Based on data from 999 patients in 7 studiesPlasma exchange has an unimportantdecrease in end stage kidney disease at1 year for those at low risk of endstage kidney disease (creatinine ≤ 200µmol/L)HighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Low to moderate ESKD risk21 fewer5029ModerateMore

Based on data from 999 patients in 7 studiesPlasma exchange probably has importantdecrease in end stage kidney disease at1 year for those at low to modearaterisk of end stage kidney disease(creatinine >200-300 µmol/L)ModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Moderate to high ESKD risk46 fewer11064ModerateMore

Based on data from 999 patients in 7 studiesPlasma exchange probably has animportant decrease in end stage kidneydisease at 1 year for those at moderateto high risk of end stage kidney disease(creatinine >300-500 µmol/L)ModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

High ESKD risk160 fewer380220HighMore

Based on data from 999 patients in 7 studiesPlasma exchange has an importantdecrease in end stage kidney disease at1 year for those at high risk of endstage kidney disease (creatinine >500µmol/L)HighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
Serious infections
At 1 yearEvents per 1000 peopleEvidence quality

Low ESKD riskNo important difference100127ModerateMore

Based on data from 908 patients in 4 studiesPlasma exchange probably has anunimportant increase in seriousinfections at 1 year for those at lowrisk of end stage kidney disease(creatinine ≤ 200 µmol/L)ModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Low to moderate ESKD riskNo important difference180229HighMore

Based on data from 908 patients in 4 studiesPlasma exchange has an unimportantincrease in serious infections at 1 yearfor those at low to modearate risk ofend stage kidney disease (creatinine>200-300 µmol/L)HighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Moderate to high ESKD risk85 fewer315400ModerateMore

Based on data from 908 patients in 4 studiesPlasma exchange probably has animportant increase in serious infectionsat 1 year for those at moderate to highrisk of end stage kidney disease(creatinine >300-500 µmol/L)ModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

High ESKD risk135 fewer500635ModerateMore

Based on data from 908 patients in 4 studiesPlasma exchange probably has animportant increase in serious infectionsat 1 year for those at high risk of endstage kidney disease (creatinine >500µmol/L)ModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes (creatinine ≤200)
See all outcomes (creatinine >200-300)
See all outcomes (creatinine >300-500)
See all outcomes (creatinine >500)
Patient decision aids (creatinine ≤300)
Patient decision aids (creatinine >300)

Individual considerations

Key practical issues The panel, taking an individual patient perspective, placed a high value on reduction in end stage kidney disease, and less value on avoiding serious infections. The panel acknowledged a likely large variation in patients’ values and preferences regarding the tradeoff between benefits (such as reduction in death or end stage kidney disease) and harms (such as increase in serious infections) Values and preferences Plasma exchange Standard care Two large peripheral intravenous lines or central venous catheters are needed, which may cause discomfort, infection, or bleeding Plasma exchange may affect the pharmacokinetics of some drugs Potential need for transfer to a centre providing plasma exchange Cost of plasma exchange is high and might not be covered by medical insurance Blood products are needed Plasma exchange devices/methods and protocols are heterogenous No additional practical issues
Recommendation 3
Standard carePlasma exchangeorPatients with pulmonaryhaemorrhage without kidneyinvolvementWe suggest immunosuppression alone without plasmaexchangeStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Rationale

The panel made this recommendation based on indirect evidence thatplasma exchange may increase the risk of serious infections (6.8%increase) but uncertain about the effect on death (1.5% reduction withvery wide 95% CI) over a time frame of 1 year.

Evidence profile

Favours standard careFavours plasma exchangeNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
At 1 yearEvents per 1000 peopleEvidence quality

Death from any causeNo important difference208193Very lowMore

Based on data from 967 patients in 6 studiesWe are uncertain whether plasma exchangeincreases or reduces death at 1 yearVery lowGRADE rating,because of:Risk of biasNo serious concernsImprecisionVery seriousIndirectnessSeriousInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Serious infections68 fewer250318.0LowMore

Based on data from 908 patients in 4 studiesPlasma exchange may have an importantincrease in serious infections at 1 yearLowGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessSeriousInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes
Patient decision aids

Individual considerations

Key practical issues The panel, taking an individual patient perspective, placed a high value on reduction in end stage kidney disease, and less value on avoiding serious infections. The panel acknowledged a likely large variation in patients’ values and preferences regarding the tradeoff between benefits (such as reduction in death or end stage kidney disease) and harms (such as increase in serious infections) Values and preferences Plasma exchange Two large peripheral intravenous lines or central venous catheters are needed, which may cause discomfort, infection, or bleeding Plasma exchange may affect the pharmacokinetics of some drugs Potential need for transfer to a centre providing plasma exchange Cost of plasma exchange is high and might not be covered by medical insurance Blood products are needed Plasma exchange devices/methods and protocols are heterogenous No additional practical issues Standard care
Recommendation 4
Standard dose glucocorticoidsReduced dose glucocorticoidsorAll patientsWe recommend reduced dose glucocorticoids ratherthan standard dose glucocorticoids during thefirst 6 months of treatmentStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Evidence profile - Severe AAV

Standard dose glucocorticoidsReduced dose glucocorticoidsNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
After more than 6 monthsEvents per 1000 peopleEvidence quality

Death21 fewer151130LowMore

Based on data from 704 patients in 1 studyReduced dose of glucocorticoids mayreduce death after more than 6 monthsLowGRADE rating,because of:Risk of biasNo serious concernsImprecisionVery seriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

End stage kidney diseaseNo important difference194198ModerateMore

Based on data from 704 patients in 1 studyReduced dose of glucocorticoids probablyhas little or no effect on end stagekidney disease after more than 6 monthsModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
6 months to 1 yearEvents per 1000 peopleEvidence quality

Serious infections59 fewer330271ModerateMore

Based on data from 704 patients in 1 studyReduced dose of glucocorticoids probablyreduces the risk of serious infectionsbetween 6 months and 1 yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes
Patient decision aids

Evidence profile - Newly diagnosed AAV

Standard dose glucocorticoidsReduced dose glucocorticoidsNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
After more than 6 monthsEvents per 1000 peopleEvidence quality

Death17 fewer4629LowMore

Based on data from 134 patients in 1 studyReduced dose of glucocorticoids mayreduce death after more than 6 monthsLowGRADE rating,because of:Risk of biasNo serious concernsImprecisionVery seriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

End stage kidney diseaseNo important difference150ModerateMore

Based on data from 134 patients in 1 studyReduced dose of glucocorticoids probablyhas little or no effect on end stagekidney disease after more than 6 monthsModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
6 months to 1 yearEvents per 1000 peopleEvidence quality

Serious infections128 fewer20072ModerateMore

Based on data from 134 patients in 1 studyReduced dose of glucocorticoids probablyreduces the risk of serious infectionsbetween 6 months and 1 yearModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes
Patient decision aids

Individual considerations

Key practical issues The panel, taking an individual patient perspective, placed a high value on reduction in end stage kidney disease, and less value on avoiding serious infections. The panel acknowledged a likely large variation in patients’ values and preferences regarding the tradeoff between benefits (such as reduction in death or end stage kidney disease) and harms (such as increase in serious infections) Values and preferences Standard dose glucocorticoids Reduced dose glucocorticoids Variable dose regimen Patients intolerant of oral glucocorticoids or for whom oral glucocorticoids are contraindicated could be given an equivalent daily IV dose Adverse events of glucocorticoids include impaired fasting glucose, loss of bone mineral density, fractures, weight gain, and mood changes

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  1. Linan Zeng, methods co-chair12,
  2. Michael Walsh, nephrologist2345,
  3. Gordon H Guyatt, methods co-chair coach, internist24,
  4. Reed A C Siemieniuk, methods co-chair coach, internist2,
  5. David Collister, patient partnership liaison, clinical scholar2345,
  6. Michelle Booth, patient partner6,
  7. Paul Brown, patient partner6,
  8. Lesha Farrar, caregiver partner7,
  9. Mark Farrar, patient partner7,
  10. Tracy Firth, patient partner7,
  11. Lynn A Fussner, pulmonologist, intensivist8,
  12. Karin Kilian, rheumatologist910,
  13. Mark A Little, nephrologist1112,
  14. Thomas A Mavrakanas, nephrologist13,
  15. Reem A Mustafa, nephrologist214,
  16. Maryam Piram, paediatrician1516,
  17. Lisa K Stamp, rheumatologist17,
  18. Yingqi Xiao, methodologist, nurse218,
  19. Lyubov Lytvyn, patient partnership liaison2,
  20. Thomas Agoritsas, methodologist, general internist219,
  21. Per O Vandvik, methodologist, general internist20,
  22. Alfred Mahr, clinical chair, rheumatologist21
  1. 1Pharmacy department/Evidence-based pharmacy centre, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
  2. 2Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
  3. 3Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  4. 4Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  5. 5St. Joseph’s Healthcare, Hamilton, Ontario, Canada
  6. 6USA
  7. 7UK
  8. 8Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  9. 9Department of Rheumatology, Oslo University Hospital, Oslo, Norway
  10. 10Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  11. 11Trinity Translational Medicine Institute, Trinity College Dublin, Ireland
  12. 12Irish Centre for Vascular Biology, Tallaght University Hospital, Dublin, Ireland
  13. 13Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
  14. 14Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas, USA
  15. 15CHU Sainte Justine Research Center, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada
  16. 16CEREMAIA, Centre d'épidémiologie et de santé des populations (CESP), University Paris-Saclay, Le Kremlin Bicêtre, France
  17. 17University of Otago Christchurch, Christchurch, New Zealand
  18. 18West China School of Nursing/Department of Nursing, West China Hospital, Sichuan University, China
  19. 19Division of General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
  20. 20Department of Medicine, Lovisenberg Hospital Trust, Oslo, Norway
  21. 21Rheumatology Clinic, Department of Internal Medicine, Kantonsspital St Gallen, St Gallen, Switzerland
  1. Correspondence to: L Zeng linanzeng{at}sina.com

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.

Footnotes

  • Funding: This guideline was not funded.

  • Competing interests: All authors have completed the BMJ Rapid Recommendations interest disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 4. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions.

  • Participation in the panel and authorship of this manuscript does not constitute organisational endorsement of the recommendations.

  • Transparency: L Zeng and A Mahr affirm that the manuscript is an honest, accurate, and transparent account of the recommendation being reported; that no important aspects of the recommendation have been omitted; and that any discrepancies from the recommendation as planned have been explained.

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