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Meta-Analysis
. 2020 Jan 13;1(1):CD003232.
doi: 10.1002/14651858.CD003232.pub4.

Interventions for renal vasculitis in adults

Giles D Walters  1 , Narelle S Willis  2   3 , Tess E Cooper  3 , Jonathan C Craig  3   4
Affiliations
Meta-Analysis

Interventions for renal vasculitis in adults

Giles D Walters et al. Cochrane Database Syst Rev. .

Abstract

Background: Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015.

Objectives: To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.

Data collection and analysis: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.

Main results: Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I2 = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I2 = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I2 = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I2 = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I2 = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I2 = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab.

Authors' conclusions: Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.

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Conflict of interest statement

None known

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Adu 1997 {published data only}
    1. Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emery P, et al. Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. Qjm 1997;90(6):401‐9. [MEDLINE: ] - PubMed
    1. Pall A, Lugmani RA, Adu D, Richards N, Howie AJ, Emery P, et al. Controlled trial of pulse cyclophosphamide (PCY) and prednisolone (PP) versus continuous cyclophosphamide (CCY) and prednisolone (CP) in the treatment of systemic vasculitis [abstract]. Journal of the American Society of Nephrology 1992;3(3):317. [CENTRAL: CN‐00461459] - PubMed
AZA‐ANCA 2016 {published data only}
    1. Sanders JF, Joode AA, DeSevaux RG, Broekroelofs J, Voskuyl AE, Paassen P, et al. Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase‐3 anti‐neutrophil cytoplasmic antibody‐associated vasculitis patients who remain cytoplasmic anti‐neutrophil cytoplasmic antibody‐positive after induction of remission: a randomized clinical trial. Nephrology Dialysis Transplantation 2016;31(9):1453‐9. [MEDLINE: ] - PubMed
Boomsma 2003 {published data only}
    1. Boomsma MM, Stegeman CA, Hermans J, Kallenberg CG, Hene RJ, Limburg PC, et al. Prevention of relapses in PR3 anti‐neutrophil cytoplasmic antibody (ANCA) associated vasculitis by treatment with azathioprine and corticosteroids: a multi‐centre, randomized study [abstract no: 020]. 11th International Vasculitis & ANCA Workshop; 2003 Oct 2‐5; Prague, Czech Republic. 2003:29‐30. [CENTRAL: CN‐00460433]
    1. Boomsma MM, Stegeman CA, Hermans J, Kallenberg CGM, Hene RJ, Limburg PC, et al. Prevention of relapses in PR3 anti‐neutrophil cytoplasmic antibody associated vasculitis by treatment with azathioprine and corticosteroids: a multi‐centre, randomized study [abstract no: T208]. Nephrology Dialysis Transplantation 2003;18(Suppl 4):347‐8. [CENTRAL: CN‐00444485]
BREVAS 2019 {published data only}
    1. Jayne D, Blockmans D, Luqmani R, Ji B, Green Y, Hall L, et al. Belimumab in combination with azathioprine for remission maintenance in granulomatosis with polyangiitis and microscopic polyangiitis: effect on biomarkers [abstract]. Annals of the Rheumatic Diseases 2018;77(Suppl 2):1488. [EMBASE: 623994409]
    1. Jayne D, Blockmans D, Luqmani R, Ji B, Green Y, Hall L, et al. Efficacy and safety of belimumab in combination with azathioprine for remission maintenance in granulomatosis with polyangiitis and microscopic polyangiitis: a multicenter randomized, placebo‐controlled study [abstract no: 893]. Arthritis and Rheumatology 2017;69(Suppl 10):NA. [EMBASE: 618912517]
    1. Jayne D, Blockmans D, Luqmani R, Moiseev S, Ji B, Green Y, et al. Efficacy and safety of belimumab and azathioprine for maintenance of remission in antineutrophil cytoplasmic antibody‐associated vasculitis: a randomized controlled study. Arthritis & Rheumatology 2019;71(6):952‐63. [MEDLINE: ] - PMC - PubMed
CLEAR 2013 {published data only}
    1. Bekker P, Jayne D, Bruchfeld A, Schaier M, Ciechanowski K, Harper L, et al. CCX168, an orally administered C5aR inhibitor for treatment of patients with antineutrophil cytoplasmic antibody‐associated vasculitis [abstract no: 1863]. Arthritis & Rheumatology 2014;66(Suppl 10):S820. [EMBASE: 71737855]
    1. Bekker P, Potarca A, Dairaghi D, Miao S, Powers JP, Jaen JC, et al. Oral C5A receptor antagonist CCX168 in a phase 2 clinical trial in ANCA‐associated renal vasculitis [abstract]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii419‐20. [EMBASE: 70766535]
    1. Bruchfeld A, Schaier M, Harper L, Jadoul MY, Segelmark M, Szombati I, et al. Phase 2 clinical trial of CCX168, an orally administered C5aR antagonist, in patients with ANCA‐associated renal vasculitis (CLEAR) [abstract no: SA‐PO695]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):788A.
    1. Bruchfeld A, Schaier M, Jadoul M, Selga D, Szombati I, Venning M, et al. C5aR inhibitor on leukocytes exploratory ANCA associated renal vasculitis (CLEAR) clinical trial with orally administered CCX168 [abstract no: P206]. Presse Medicale 2013;42(4):768. [EMBASE: 71944014]
    1. Bunch DO, McInnis EA, Bekker P, Hillson JL, Schall TJ, Jennette CJ, et al. Effect of a selective C5AR antagonist, avacopan (CCX168), on plasma complement levels in ANCA associated vasculitis (AAV) [abstract]. Annals of the Rheumatic Diseases 2018;77(Suppl 2):74‐5. [EMBASE: 623992027]
Cole 1992 {published data only}
    1. Cole E, Cattran D, Magil A, Greenwood C, Churchill D, Sutton D, et al. A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. American Journal of Kidney Diseases 1992;20(3):261‐9. [MEDLINE: ] - PubMed
CORTAGE 2015 {published data only}
    1. Pagnoux C, Quemeneur T, Ninet J, Diot E, Kyndt X, Wazieres B, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty‐five years or older: results of a multicenter, open‐label, randomized controlled trial of corticosteroid and cyclophosphamide‐based induction therapy. Arthritis & Rheumatology 2015;67(4):1117‐27. [MEDLINE: ] - PubMed
    1. Pagnoux C, Rollot F, Vanhille P, Ninet J, Diot E, Kyndt X, et al. Baseline data and interim induction analysis based on the 101 patients aged ≥ 65 years with SNV enrolled in the CORTAGE multi‐centre trial [abstract]. Clinical & Experimental Immunology 2011;164(Suppl 1):63. [EMBASE: 70622655]
CYCAZAREM 2003 {published data only}
    1. Flossmann O, Jayne DR. Demographic data in ANCA associated vasculitis [abstract no: 90]. Kidney & Blood Pressure Research 2005;28(3):189. [CENTRAL: CN‐00583623]
    1. Flossmann O, Jayne DR. Demographic data in ANCA associated vasculitis [abstract no: F‐PO998]. Journal of the American Society of Nephrology 2005;16:554A. [CENTRAL: CN‐01912399]
    1. Goceroglu A, Berden AE, Fiocco M, Flosmann O, Westman KW, Ferrario F, et al. ANCA‐associated glomerulonephritis: risk factors for renal relapse. PLoS ONE [Electronic Resource] 2016;11(12):e0165402. [MEDLINE: ] - PMC - PubMed
    1. Goek ON, Stone JH. Randomized controlled trials in vasculitis associated with anti‐neutrophil cytoplasmic antibodies. Current Opinion in Rheumatology 2005;17(3):257‐64. [MEDLINE: ] - PubMed
    1. Harper L, Verburgh K, Savage CO, Jayne D. Adverse events in patients with primary systemic vasculitis [abstract no: SA‐PO271]. Journal of the American Society of Nephrology 2004;15(Oct):360A. [CENTRAL: CN‐00583612]
CYCLOPS 2004 {published data only}
    1. Harper L, Morgan M, Flossman O, Westman K, Groot K, Flores Suarez LF, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA‐associated vasculitis [abstract no: 079]. Renal Association & British Renal Society Joint Meeting; 2011 Jun 6‐9; Birmingham, UK. 2011:908.
    1. Harper L, Morgan MD, Flossman O, Westman K, Groot K, Flores Suarez LF, et al. Pulse versus daily oral CyP for induction of remission in ANCA‐associated vasculitis. A European, multi‐centre randomized controlled trial: long‐term follow up [abstract]. Clinical & Experimental Immunology 2011;164(Suppl 1):56. [EMBASE: 70622641]
    1. Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA‐associated vasculitis: long‐term follow‐up. Annals of the Rheumatic Diseases 2012;71(6):955‐60. [MEDLINE: ] - PubMed
    1. Morgan MD, Szeto M, Marsh J, Walsh M, Jayne D, Westman K, et al. Remaining anti‐neutrophil cytoplasm antibody positive at switch to maintenance therapy is associated with an increased risk of relapse: observation from the long term follow up of the CYCLOPS and IMPROVE trials [abstract no: P20]. Nephron 2015;129(Suppl 2):115. [EMBASE: 623780483]
    1. Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, et al. Negative anti‐neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Research & Therapy 2017;19(1):129. [EMBASE: 616622020] - PMC - PubMed
Furuta 1998 {published data only}
    1. Furuta T, Hotta O, Chiba S, Horigome I, Taguma Y. Lymphocytapheresis (LCP) in rapidly progressive glomerulonephritis (RPGN) a comparison with steroid pulse therapy [abstract no: P208]. Nephrology 1997;3(Suppl 1):S127. [CENTRAL: CN‐00460781]
    1. Furuta T, Hotta O, Yusa N, Horigome I, Chiba S, Taguma Y. Lymphocytapheresis to treat rapidly progressive glomerulonephritis: a randomised comparison with steroid‐pulse treatment. Lancet 1998;352(9123):203‐4. [MEDLINE: ] - PubMed
Glockner 1988 {published data only}
    1. Glockner WM, Sieberth HG, Wichmann HE, Backes E, Bambauer R, Boesken WH, et al. Plasma exchange and immunosuppression in rapidly progressive glomerulonephritis: a controlled, multi‐center study. Clinical Nephrology 1988;29(1):1‐8. [MEDLINE: ] - PubMed
Guillevin 1997 {published data only}
    1. Girard T, Mahr A, Noel LH, Cordier JF, Lesavre P, Andre MH, et al. Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study. Rheumatology 2001;40(2):147‐51. [MEDLINE: ] - PubMed
    1. Gottenberg JE, Mahr A, Pagnoux C, Cohen P, Mouthon L, Guillevin L, et al. Long‐term outcome of 37 patients with Wegener's granulomatosis with renal involvement. Presse Medicale 2007;36(5 Pt 1):771‐8. [MEDLINE: ] - PubMed
    1. Guillevin L, Cordier JF, Lhote F, Cohen P, Jarrousse B, Royer I, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis. Arthritis & Rheumatism 1997;40(12):2187‐98. [MEDLINE: ] - PubMed
Guillevin 2003 {published data only}
    1. Guillevin L, Cohen P, Mahr A, Arene JP, Mouthon L, Puechal X, et al. Treatment of polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA) with poor prognosis factors: a prospective trial comparing steroids (CS) and 6 or 12 cyclophosphamide (CYC) pulses in 65 patients [abstract no: 112‐113]. Cleveland Clinic Journal of Medicine 2002;69(Suppl II):SII‐189. [CENTRAL: CN‐01912272]
    1. Guillevin L, Cohen P, Mahr A, Arene JP, Mouthon L, Puechal X, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty‐five patients. Arthritis & Rheumatism 2003;49(1):93‐100. [MEDLINE: ] - PubMed
Han 2011b {published data only}
    1. Han F, Liu G, Zhang X, Li Xi, He Q, He X, et al. Effects of mycophenolate mofetil combined with corticosteroids for induction therapy of microscopic polyangiitis. American Journal of Nephrology 2011;33(2):185‐92. [MEDLINE: ] - PubMed
Haubitz 1998 {published data only}
    1. Haubitz M, Brunkhorst R, Schellong S, Gobel U, Schurek HJ, Koch KM. ANCA‐associated vasculitis and renal involvement: preliminary results of a prospective randomised study comparing daily oral versus monthly I.V. cyclophosphamide application [abstract]. Journal of the American Society of Nephrology 1995;6(3):922. [CENTRAL: CN‐00484270]
    1. Haubitz M, Schellong S, Gobel U, Schurek HJ, Schaumann D, Koch KM, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody‐associated vasculitis and renal involvement: a prospective, randomized study. Arthritis & Rheumatism 1998;41(10):1835‐44. [MEDLINE: ] - PubMed
Hu 2008b {published data only}
    1. Hu W, Liu C, Xie H, Chen H, Liu Z, Li L. Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement. Nephrology Dialysis Transplantation 2008;23(4):1307‐12. [MEDLINE: ] - PubMed
IMPROVE 2003 {published data only}
    1. Hiemstra T, Walsh M, Andrews P, Short A, Savage C, Harper L, et al. Randomized controlled trial of mycophenolate mofetil versus azathioprine for maintenance therapy in ANCA‐associated vasculitis (IMPROVE) [abstract no: O23]. British Renal Society Conference; 2010 May 17‐May 20; Manchester, UK. 2010. [CENTRAL: CN‐01912269]
    1. Hiemstra TF, Walsh M, Mahr A, Savage CO, Groot K, Harper L, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody‐associated vasculitis: a randomized controlled trial. JAMA 2010;304(21):2381‐8. [MEDLINE: ] - PubMed
    1. Hiemstra TF, Walsh MW, Schmitt W, Jayne DR. Randomised controlled trial of mycophenolate mofetil versus azathioprine for maintenance therapy in ANCA associated vasculitis (IMPROVE) [abstract no: SA‐FC331]. Journal of the American Society of Nephrology 2009;20(Abstracts):77A. [CENTRAL: CN‐01912270]
    1. IMPROVE Co‐ordinators. International mycophenolate mofetil protocol to reduce outbreaks of vasculitides (IMPROVE). www.vasculitis.org/images/documents/improve.pdf (accessed 16 December 2019).
    1. Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, et al. Negative anti‐neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Research & Therapy 2017;19(1):129. [MEDLINE: ] - PMC - PubMed
Jayne 2000 {published data only}
    1. Jayne DR, Chapel H, Adu D, Misbah S, O'Donoghue D, Scott D, et al. Intravenous immunoglobulin for ANCA‐associated systemic vasculitis with persistent disease activity. Qjm 2000;93(7):433‐9. [MEDLINE: ] - PubMed
MAINRITSAN 2014 {published data only}
    1. Guillevin L, Karras A, Pagnoux C, Carron P, Quemeneur T, Gobert P, et al. Rituximab versus azathioprine for maintenance in ANCA‐associated vasculitis. A prospective study in 117 patients [abstract]. Nephrology Dialysis Transplantation 2014;29(Suppl 3):iii28. [EMBASE: 71491532]
    1. Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, et al. Rituximab versus azathioprine for maintenance in ANCA‐associated vasculitis. New England Journal of Medicine 2014;371(19):1771‐80. [MEDLINE: ] - PubMed
    1. Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, et al. Rituximab versus azathioprine for maintenance in antineutrophil cytoplasmic antibodies (ANCA)‐associated vasculitis [abstract]. Arthritis & Rheumatism 2012;64(10 Suppl):S706. [EMBASE: 70999648]
    1. Guillevin TL, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, et al. Relationship between infectious side effects and immunoglobulin levels in the maintenance rituximab vs azathioprine for ANCA‐associated vasculitides [abstract no: 744]. Arthritis & Rheumatism 2013;65(10 Suppl):S314. [EMBASE: 71318224]
    1. Montante A, Bras A, Terrier B, Cohen P, Puechal X, Karras A, et al. Economic evaluation of rituximab versus azathioprine for maintenance treatment of ANCA‐associated vasculitis. A prospective, multicenter study [abstract]. Arthritis & Rheumatology 2017;69(Suppl 10):na. [EMBASE: 618916781]
MAINRITSAN 2 2018 {published data only}
    1. Charles P, Dechartres A, Terrier B, Guillevin L. Reducing the number of rituximab infusions at onset of maintenance therapy for ANCA‐associated vasculitides: results of a post hoc analysis from a randomized‐controlled trials [abstract]. Rheumatology 2019;58(Suppl 2):na. [EMBASE: 628291931]
    1. Charles P, Terrier B, Cohen P, Faguer S, Huart A, Hamidou M, et al. Comparison of systematic vs individually tailored rituximab regimen to maintain ANCA associated vasculitis remission [abstract]. Rheumatology 2017;56(Suppl 3):iii151. [EMBASE: 619334915]
    1. Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, et al. Comparison of individually tailored versus fixed‐schedule rituximab regimen to maintain ANCA‐associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).[Erratum appears in: Ann Rheum Dis. 2019 Sep;78(9):e101; PMID: 31405899]. Annals of the Rheumatic Diseases 2018;77(8):1143‐9. [MEDLINE: ] - PubMed
    1. Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, et al. Comparison of individually tailored vs systematic rituximab regimens to maintain ANCA‐associated vasculitis remissions: results of a prospective, randomized‐controlled, phase 3 trial [abstract]. Arthritis & Rheumatology 2017;69(Suppl 10). [EMBASE: 618916722]
Maritati 2017 {published data only}
    1. Maritati F, Alberici F, Oliva E, Urban ML, Palmisano A, Santarsia F, et al. Methotrexate versus cyclophosphamide for remission maintenance in ANCA‐associated vasculitis: a randomised trial. PLoS ONE [Electronic Resource] 2017;12(10):e0185880. [MEDLINE: ] - PMC - PubMed
    1. Vaglio A, Casazza I, Grasselli C, Alberici F, Palmisano A, Andrulli S, et al. Methotrexate versus cyclophosphamide as maintenance therapy for ANCA‐associated vasculitides [abstract no: M318]. World Congress of Nephrology; 2009 May 22‐26; Milan, Italy. 2009.
Mauri 1985 {published data only}
    1. Mauri JM, Gonzalez MT, Poveda R. Therapeutic plasma exchange in the treatment of rapidly progressive glomerulonephritis. Plasma Therapy & Transfusion Technology 1985;6(3):587‐91. [EMBASE: 1986054364]
    1. Mauri JM, Gonzalez R, Poveda R, Seron D, Torras J, Andres E. Evaluation of plasma exchanges (PEX) in the treatment of rapidly progressive glomerulonephritis (RPGN) preliminary results of a randomized trial [abstract no: 231]. European Journal of Clinical Investigation 1985;15(2 (Pt II)):A39. [CENTRAL: CN‐00446666]
MEPEX 2007 {published data only}
    1. Casian A. Plasma exchange for severe renal vasculitis: long‐term follow‐up of the MEPEX trial [abstract]. Clinical & Experimental Immunology 2011;164(Suppl 1):52. [EMBASE: 70622633]
    1. Casian AL, Walsh M, Jayne DR. A long‐term analysis of the MEPEX trial: plasma exchange for severe renal ANCA vasculitis [abstract no: FR‐OR290]. Journal of the American Society of Nephrology 2011;22(Abstract Suppl):70A.
    1. Flossmann O, Jayne DR. Demographic data in ANCA associated vasculitis [abstract no: 90]. Kidney & Blood Pressure Research 2005;28(3):189. [CENTRAL: CN‐00583623]
    1. Flossmann O, Jayne DR. Demographic data in ANCA associated vasculitis [abstract]. Journal of the American Society of Nephrology 2005;16(Abstracts):554A. [CENTRAL: CN‐01912399]
    1. Gaskin G, Jayne DR, European Vasculitis Study Group. Adjunctive plasma exchange is superior to methylprednisolone in acute renal failure due to ANCA‐associated glomerulonephritis [abstract no: F‐FC010]. Journal of the American Society of Nephrology 2002;13(Programs & Abstracts):2A. [CENTRAL: CN‐00445448]
Metzler 2007 {published data only}
    1. Metzler C, Miehle N, Manger K, Iking‐Konert C, Gross WL, Reinhold‐Keller E. Unexpected high relapse‐rate under oral methotrexate for maintenance of remission in Wegener's granulomatosis. The LEM‐trial comparing leflunomide versus methotrexat [abstract no: 106]. Kidney & Blood Pressure Research 2005;28:196. [CENTRAL: CN‐00653812]
    1. Metzler C, Miehle N, Manger K, Iking‐Konert C, Groot K, Hellmich B, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis. Rheumatology 2007;46(7):1087‐91. [MEDLINE: ] - PubMed
MYCYC 2012 {published data only}
    1. Jayne D, Jones R, Harper L. MYCYC clinical trial protocol: A randomised clinical trial of mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA associated vasculitis [protocol Version 2A, 16th January 2007]. www.vasculitis.org/images/documents/mycyc.pdf (accessed 1 December 2019).
    1. Jones R, Harper L, Brogan P, Dahisveen K, Lanyon P, Jayne D. A randomised trial of mycophenolate mofetil versus cyclosphosphamide for remission induction of ANCA‐associated vasculitis: MYCYC [abstract no: O4]. British Transplantation Society & the Renal Association Joint Congress; 2013 Mar 13‐15; Bournemouth, UK. 2013.
    1. Jones R, Walsh M, European Vascular Study Group. A randomised trial of mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA‐associated vasculitis: MYCYC [abstract no: HI‐OR04]. Journal of the American Society of Nephrology 2012;23(Abstracts):3B. [CENTRAL: CN‐01912277]
    1. Jones RB, Harper L, Walsh M, Jayne DR. 18 month results from a randomised trial of mycophenolate mofetil versus cyclophosphamide for remission induction of severe ANCA‐associated vasculitis: MYCYC [abstract no: SA‐PO1077]. Journal of the American Society of Nephrology 2013;24(Abstract Suppl):2B.
    1. Jones RB, Hiemstra TF, Ballarin J, Blockmans DE, Brogan P, Bruchfeld A, et al. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA‐associated vasculitis: a randomised, non‐inferiority trial. Annals of the Rheumatic Diseases 2019;78(3):399‐405. [MEDLINE: ] - PubMed
NORAM 2005 {published data only}
    1. Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody‐associated vasculitis. Arthritis & Rheumatism 2005;52(8):2461‐9. [MEDLINE: ] - PubMed
    1. Faurschou M, Westman K, Rasmussen N, Groot K, Flossmann O, Hoglund P, et al. Brief Report: long‐term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody‐associated vasculitis. Arthritis & Rheumatism 2012;64(10):3472‐7. [MEDLINE: ] - PubMed
    1. Goek ON, Stone JH. Randomized controlled trials in vasculitis associated with anti‐neutrophil cytoplasmic antibodies. Current Opinion in Rheumatology 2005;17(3):257‐64. [MEDLINE: ] - PubMed
    1. Rasmussen N, Salmela A, Ekstrand A, Groot K, Gregorini G, Cohen Tervaert JW, et al. Changes in proteinase 3 anti‐neutrophil cytoplasm autoantibody levels in early systemic granulomatosis with polyangiitis (Wegener's) may reflect treatment rather than disease activity. Clinical & Experimental Rheumatology 2013;31(1 Suppl 75):S38‐44. [MEDLINE: ] - PubMed
    1. Salmela A, Rasmussen N, Tervaert JW, Jayne DR, Ekstrand A, European Vasculitis Study Group. Chronic nasal Staphylococcus aureus carriage identifies a subset of newly diagnosed granulomatosis with polyangiitis patients with high relapse rate. Rheumatology 2017;56(6):965‐72. [MEDLINE: ] - PubMed
PEXIVAS 2013 {published data only}
    1. Casian A, Merkel P, Walsh M, Jayne D. PEXIVAS: design of a randomised controlled trial of plasma exchange and glucocorticoid dosing in severe ANCA associated vasculitis [abstract no: P259]. Renal Association & British Renal Society Joint Meeting; 2010 May 17‐20; Manchester, UK. 2010:363.
    1. European Vasculitis Study Group (EUVAS) and the Vasculitis Clinical Research Consortium (VCRC). Plasma exchange and glucocorticoid dosing in the treatment of anti‐neutrophil cytoplasm antibody associated vasculitis: an international randomized controlled trial (Protocol Version: 1.1). 2010. www.vasculitis.org/images/pexivas201.120protocol.pdf (accessed prior to 16 December 2019).
    1. Kono H, Uchida S, Muso E, Endo T, Kakita H, Hamano Y, et al. Demographic characteristics of Japanese participants in PEXIVAS as compared with REMIT‐JAV [abstract]. Rheumatology 2017;56(Suppl 3):iii150. [EMBASE: 619334902]
    1. Walsh M, Merkel P, Casian A, Jayne D. PEXIVAS: design of an RCT of PLEX and GC dosing in the treatment of severe ANCA‐AAV [abstract]. Clinical & Experimental Immunology 2011;164(Suppl 1):67. [EMBASE: 70622662]
    1. Walsh M, Merkel P, Peh CA, Guillevin L, Fujimoto S, Ives N, et al. Plasma exchange and glucocorticoid dosing in the treatment of anti‐neutrophil cytoplasm antibody associated vasculitis: Baseline characteristics of a randomized controlled trial (PEXIVAS) [abstract]. Rheumatology 2017;56(Suppl 3):iii149. [EMBASE: 619334895]
Pusey 1991 {published data only}
    1. Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM. Plasma exchange in focal necrotizing glomerulonephritis without anti‐GBM antibodies. Kidney International 1991;40(4):757‐63. [MEDLINE: ] - PubMed
RAVE 2010 {published data only}
    1. Abdulahad WH, Specks U, Bijma T, Phippard DJ, Karnell F, Lim N, et al. B‐cell depletion by rituximab affects the distribution of effector th‐cell subsets in patients with ANCA associated vasculitis [abstract]. Arthritis & Rheumatology 2017;69(Suppl 10):na. [EMBASE: 618916466]
    1. Berti A, Warner R, Johnson K, Cornec D, Schroder D, Kabat B, et al. Circulating cytokine profiles reflect ANCA specificity in patients with ANCA‐associated vasculitis [abstract]. Arthritis & Rheumatology 2017;69(Suppl 10):na. [EMBASE: 618916561] - PMC - PubMed
    1. Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B, et al. Serum interleukin‐6 levels in antineutrophil cytoplasmic antibody‐associated vasculitis [abstract]. Annals of the Rheumatic Diseases 2018;77(Suppl 2):771. [EMBASE: 623991960]
    1. Cartin‐Ceba R, Indrakanti D, Fervenza F, Hoffman G, Kallenberg C, Langford C, et al. Association of Fc gamma receptor polymorphisms and outcomes in patients with ANCA‐associated vasculitis treated with rituximab [abstract no: O84]. Nephron 2015;129(Suppl 2):96. [CENTRAL: CN‐01912275]
    1. Clain J, Specks U, Stone J. The association of IgM ANCA and alveolar hemorrhage revisited [abstract no: P9]. Presse Medicale 2013;42(4 Pt 2):685. [EMBASE: 71943818]
REMAIN 2003 {published data only}
    1. European Vasculitis Study Group (EUVAS). Clinical trial protocol ‐ REMAIN ‐ Randomised trial of prolonged remission‐maintenance therapy in systemic vasculitis [Version 4.2: January 2006]. www.vasculitis.nl/media/documents/remain.pdf (accessed 17 December 2019).
    1. Karras A, Pagnoux C, Haubitz M, Groot K, Puechal X, Tervaert JWC, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA‐associated vasculitis. Annals of the Rheumatic Diseases 2017;76(10):1662‐8. [MEDLINE: ] - PubMed
    1. Karras A, Segelmark M, Jayne DR. Randomized controlled trial of treatment withdrawal in the remission phase of ANCA vasculitis: the REMAIN study [abstract no: TH‐OR025]. Journal of the American Society of Nephrology 2015;26(Abstract Suppl):7a.
Rifle 1980 {published data only}
    1. Rifle G, Chalopin JM, Zech P, Deteix P, Ducret F, Vialtel P, et al. Treatment of idiopathic acute crescentic glomerulonephritis by immunodepression and plasma‐exchanges. A prospective randomised study. Proceedings of the European Dialysis & Transplant Association 1981;18:493‐502. [MEDLINE: ] - PubMed
RITUXVAS 2010 {published data only}
    1. Berden AE, Jones RB, Erasmus DD, Walsh M, Noel LH, Ferrario F, et al. Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody‐associated glomerulonephritis after rituximab therapy. Journal of the American Society of Nephrology 2012;23(2):313‐21. [MEDLINE: ] - PubMed
    1. Jayne DR, Jones R. An international, randomised open label trial comparing a rituximab based regime with a standard cyclophosphamide/azathioprine regimen in the treatment of active 'generalised' ANCA‐associated vasculitis [protocol v1b Nov 2005]. www.vasculitis.nl/media/documents/rituxvas.pdf (accessed 1 December 2019).
    1. Jones R, Savage C, Peh CA, Hauser T, Cohen Tervaert JW, Tesar V, et al. Rituximab: a novel remission induction agent in ANCA associated vasculitis: the design of an international, randomised trials (RITUXVAS) [abstract no: PUB647]. Journal of the American Society of Nephrology 2007;18(Abstracts):972A. [CENTRAL: CN‐01912265]
    1. Jones R, Tervaert J, Hauser T, Luqmani R, Morgan M, Peh C, et al. Two year follow‐up results from a randomised trial of rituximab versus cyclophosphamide for ANCA‐associated renal vasculitis: RITUXVAS [abstract]. Renal Association & British Renal Society Joint Meeting; 2011 Jun 6‐9 ; Birmingham, UK. 2011:1157.
    1. Jones R, Tervaert JW, Hauser T, Luqmani R, Peh CA, Savage C, et al. A randomised trial of rituximab versus cyclophosphamide for ANCA‐associated renal vasculitis: RITUXVAS [abstract no: SA773]. World Congress of Nephrology; 2009 May 22‐26; Milan, Italy. 2009. [CENTRAL: CN‐01912295]
Stegeman 1996 {published data only}
    1. Stegeman CA, Cohen Tervaert JW, Jong PE, Kallenberg CG. Prevention of relapses of Wegener's granulomatosis by treatment with co‐trimoxazole. A placebo controlled trial [abstract]. Journal of the American Society of Nephrology 1995;6(3):930. [CENTRAL: CN‐00486000]
    1. Stegeman CA, Tervaert JW, Jong PE, Kallenberg CG. Trimethoprim‐sulfamethoxazole (co‐trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co‐Trimoxazole Wegener Study Group. New England Journal of Medicine 1996;335(1):16‐20. [MEDLINE: ] - PubMed
Stegmayr 1999 {published data only}
    1. Stegmayr BG, Almroth G, Berlin G, Fehrman I, Kurkus J, Norda R, et al. Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi‐center study. International Journal of Artificial Organs 1999;22(2):81‐7. [MEDLINE: ] - PubMed
    1. Stegmayr BG, Almroth G, Kurkus J, Olander R, Sterner G, Thysell H, et al. Plasma exchange versus immunoadsorption in the treatment of rapidly progressive glomerulonephritis (RPG). A multi‐center study [abstract]. XXXV Congress of the European Renal Association European Dialysis & Transplant Association; 1998 Jun 6‐9; Rimini (Italy). 1998:294. [CENTRAL: CN‐00486001]
Szpirt 2011 {published data only}
    1. Szpirt WM, Heaf JG, Petersen J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener's granulomatosis‐‐a clinical randomized controlled trial. Nephrology Dialysis Transplantation 2011;26(1):206‐13. [MEDLINE: ] - PubMed
    1. Szpirt WM, Rasmussen N, Petersen J. Long term outcome and prognostic factors in randomized study of plasma exchange and cyclosporin‐A in Wegener's granulomatosis [abstract no: A0932]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):182A. [CENTRAL: CN‐01912294]
    1. Szpirt WM, Rasmussen N, Petersen J. Plasma exchange and cyclosporin A in Wegner`s granulomatosis a controlled study [abstract]. International Journal of Artificial Organs 1996;19(9):501. [CENTRAL: CN‐00322008]
    1. Szpirt WM, Rasmussen N, Petersen J. Plasma exchange for induction and cyclosporin A for maintenance of remission in Wegener's granulomatosis [abstract no: A2677]. Journal of the American Society of Nephrology 1996;7(9):1781. [CENTRAL: CN‐01912292]
Tervaert 1990 {published data only}
    1. Tervaert JW, Huitema MG, Hene RJ, Sluiter WJ, The TH, Hem GK, et al. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet 1990;336(8717):709‐11. [MEDLINE: ] - PubMed
WEGENT 2008 {published data only}
    1. Mahr A, Pagnoux C, Cohen C, Hamidou M, Ruivard M, Mouthon L, et al. Treatment of ANCA‐associated vasculitides: corticosteroids and pulse cyclophosphamide followed by maintenance therapy with methotrexate or azathioprine: a prospective multicenter randomized trial (WEGENT) [abstract no: 102]. Kidney & Blood Pressure Research 2005;28(3):194. [CENTRAL: CN‐01912293]
    1. Pagnoux C, Mahr A, Cohen P, Arene JP, Hamidou M, Guillevin L, et al. Treatment of ANCA‐associated systemic vasculitis (AASV) with corticosteroids (CS) and pulse cyclophosphamide (CYC), then azathioprine (AZA) or methotrexate (MTX) to maintain remission: interim analysis [abstract]. 11th International Vasculitis & ANCA Workshop; 2003 Oct 2‐5; Prague, Czech Republic. 2003:47. [CENTRAL: CN‐00461458]
    1. Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, et al. Azathioprine or methotrexate maintenance for ANCA‐associated vasculitis. New England Journal of Medicine 2008;359(26):2790‐803. [MEDLINE: ] - PubMed
    1. Puechal X, Pagnoux C, Perrodeau E, Hamidou M, Boffa JJ, Kyndt X, et al. Granulomatosis with polyangiitis or microscopic polyangiitis: long term outcomes of the prospective WEGENT trial comparing azathioprine vs methotrexate for remission maintenance in 126 patients [abstract no: O60]. Nephron 2015;129(Suppl 2):80. [EMBASE: 623780460]
    1. Puechal X, Pagnoux C, Perrodeau E, Hamidou M, Boffa JJ, Kyndt X, et al. Long‐term outcomes among participants in the WEGENT trial of remission‐maintenance therapy for granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis. Arthritis & Rheumatology 2016;68(3):690‐701. [MEDLINE: ] - PubMed
WGET 2002 {published data only}
    1. Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, Clair EW, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Annals of Internal Medicine 2007;147(9):611‐9. [MEDLINE: ] - PubMed
    1. Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, Clair EW, et al. Glycosylation of proteinase 3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. Clinical & Experimental Rheumatology 2009;27(1 Suppl 52):S45‐52. [MEDLINE: ] - PMC - PubMed
    1. Goek ON, Stone JH. Randomized controlled trials in vasculitis associated with anti‐neutrophil cytoplasmic antibodies. Current Opinion in Rheumatology 2005;17(3):257‐64. [MEDLINE: ] - PubMed
    1. Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Annals of Internal Medicine 2005;142(8):620‐6. [MEDLINE: ] - PubMed
    1. Rhee RL, Davis JC, Ding L, Fervenza FC, Hoffman GS, Kallenberg CG, et al. The utility of urinalysis in determining the risk of renal relapse in ANCA‐associated vasculitis. Clinical Journal of the American Society of Nephrology: CJASN 2018;13(2):251‐7. [MEDLINE: ] - PMC - PubMed
Zauner 2002 {published data only}
    1. Bohler J, Zauner I, Bach D, Braun N, Funfstuck R, Helmchen U, et al. Effect of initial histology and plasmapheresis treatment on prognosis of RPGN: results of the German prospective randomized multicenter study [abstract no: 947]. Journal of the American Society of Nephrology 1995;6(3):412. [CENTRAL: CN‐00483280]
    1. Zauner I, Bach D, Braun N, Kramer BK, Funfstuck R, Helmchen U, et al. Predictive value of initial histology and effect of plasmapheresis on long‐term prognosis of rapidly progressive glomerulonephritis. American Journal of Kidney Diseases 2002;39(1):28‐35. [MEDLINE: ] - PubMed
    1. Zauner I, Bach D, Braun N, Kramer BK, Funfstuck R, Helmchen U, et al. Ten year follow up after treatment for rapidly progressive glomerulonephritis. Results from the German prospective randomized multicenter study [abstract no: A0918]. Journal of the American Society of Nephrology 2000;11(Sept):172A. [CENTRAL: CN‐00550632]
Zycinska 2009 {published data only}
    1. Zycinska K, Wardyn KA, Zielonka TM, Krupa R, Lukas W. Co‐trimoxazole and prevention of relapses of PR3‐ANCA positive vasculitis with pulmonary involvement. European Journal of Medical Research 2009;14 Suppl 4:265‐7. [MEDLINE: ] - PMC - PubMed

References to studies excluded from this review

Basu 2017 {published data only}
    1. Basu G, Beasley M, Jones GT, Druce K, D'Allesandro M, Moffat H, et al. Psychological interventions delivered by allied health professionals (AHPS) can improve quality of life in patients with inactive ANCA associated vasculitis: results from a pilot randomised trial [abstract]. Rheumatology 2017;56(Suppl 3):iii164. [EMBASE: 619334569]
CHUSPAN 2 2017 {published data only}
    1. Puechal X, Pagnoux C, Baron G, Quemeneur T, Neel A, Agard C, et al. Adding azathioprine to remission‐induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg‐Strauss), microscopic polyangiitis, or polyarteritis nodosa without poor prognosis factors: a randomized, controlled trial. Arthritis & Rheumatology 2017;69(11):2175‐86. [MEDLINE: ] - PubMed
De Vita 2012 {published data only}
    1. Vita S, Quartuccio L, Isola M, Masolini P, Sacco S, Marchi G, et al. A randomized, controlled, multicenter phase III study of the efficacy and safety of rituximab (RTX) monotherapy versus the best available treatment in patients with mixed cryoglobulinemia syndrome [abstract]. Arthritis & Rheumatism 2010;62(Suppl 10):2201. [EMBASE: 70380187]
    1. Vita S, Quartuccio L, Isola M, Mazzaro C, Scaini P, Lenzi M, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis & Rheumatism 2012;64(3):843‐53. [MEDLINE: ] - PubMed
    1. Vita S, Quartuccio L, Masolini P, Stefania S, Marchi G, Zabotti A, et al. A randomized, controlled, multicenter phase III study of the efficacy and safety of rituximab (RTX) monotherapy versus the best available treatment (BAT) in patients with mixed cryoglobulinemia syndrome [abstract no: OP0120]. Annals of Rheumatic Diseases 2010;69(Suppl 3):93.
    1. Quartuccio L, Zuliani F, Corazza L, Scaini P, Zani R, Lenzi M, et al. Retreatment regimen of rituximab monotherapy given at the relapse of severe HCV‐related cryoglobulinemic vasculitis: long‐term follow up data of a randomized controlled multicentre study. Journal of Autoimmunity 2015;63:88‐93. [MEDLINE: ] - PubMed
    1. Quartuccio L, Zuliani F, Corazza L, Scaini P, Zani R, Lenzi M, et al. Rituximab monotherapy of severe HCV‐related cryoglobulinemic vasculitis for more than 2 years: follow‐up of a randomized controlled multicentre study [abstract no: OP0228]. Annals of the Rheumatic Diseases 2014;73(Suppl 2). [EMBASE: 71551183]
Harper 2018 {published data only}
    1. Harper L, Morgan MD, Chanouzas D, Caulfield HK, Coughlan L, Dean C, et al. Treatment of fatigue with physical activity and behavioural change support in vasculitis: study protocol for an open‐label randomised controlled feasibility study. BMJ Open 2018;8(10):e023769. [MEDLINE: ] - PMC - PubMed
Imai 2006 {published data only}
    1. Imai H, Hotta O, Yoshimura M, Konta T, Tsubakihara Y, Miyazaki M, et al. Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open‐label trial to evaluate safety and efficacy. Clinical & Experimental Nephrology 2006;10(1):40‐54. [MEDLINE: ] - PubMed
Ribi 2010 {published data only}
    1. Ribi C, Cohen P, Pagnoux C, Mahr A, Arene JP, Puechal X, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis without poor‐prognosis factors: a prospective randomized study of one hundred twenty‐four patients. Arthritis & Rheumatism 2010;62(4):1186‐97. [MEDLINE: ] - PubMed
Rifle 1990 {published data only}
    1. Rifle G, Dechelette E. Treatment of rapidly progressive glomerulonephritis by plasma exchange and methylprednisolone pulses. A prospective randomized trial of cyclophosphamide. Interim analysis. The French Cooperative Group. Progress in Clinical & Biological Research 1990;337:263‐7. [MEDLINE: ] - PubMed

References to studies awaiting assessment

Chen 2011c {published data only}
    1. Chen N, Li X, Zhang W, Shen P, Yu H, Chen Y, et al. A randomized controlled trial of mycophenolate mofetil versus cyclophosphamide for induction therapy in ANCA associated systemic vasculitis with renal involvement [abstract]. Nephrology Dialysis Transplantation 2012;27:ii61‐2. [EMBASE: 70765469]
    1. Chen N, Yu H, Zhang W, Ren H, Shen P, Li X, et al. A randomized controlled trial of MMF versus CyP for induction therapy in ANCA‐ AASV with renal involvement [abstract]. Clinical & Experimental Immunology 2011;164(Suppl 1):52‐3. [EMBASE: 70622634]
CLASSIC 2016 {published data only}
    1. Merkel PA, Niles J, Jimenez R, Spiera RF, Rovin BH, Bomback A, et al. A randomized clinical trial of CCX168, an orally administered C5AR inhibitor for treatment of patients with ANCA‐associated vasculitis [abstract no: 978]. Arthritis & Rheumatology 2016;68(Suppl 10):1296‐7. [EMBASE: 613887152]
    1. Schall T, Potarca A, Hillson J, Bekker P. C5aR inhibitor avacopan in anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis phase II outcomes of safety, renal parameters, and quality of life [abstract]. American Journal of Kidney Diseases 2018;71(4):582. [EMBASE: 621595967]
Henderson 2009 {published data only}
    1. Henderson S, Salama AD, EUVAS Study Group. CTLA4‐Ig in the treatment of ANCA‐associated vasculitis [abstract no: F‐PO1308]. Journal of the American Society of Nephrology 2009;20(Abstract Suppl):412A.
MAINTANCAVAS 2017 {published data only}
    1. Cortazar FB, Pendergraft WF, Dunbar CB, Laliberte KA, Niles J. Design of the maintenance of ANCA vasculitis remission by intermittent rituximab dosing based on B cell reconstitution versus a serologic ANCA flare (MAINTANCAVAS) trial [abstract no: SA‐PO257]. Journal of the American Society of Nephrology 2017;28(Abstract Suppl):744.
Pagnoux 2003 {published data only}
    1. Pagnoux C, Cohen P, Mahr A, Hauser T, Mouthon L, Arene JP, et al. Treatment of Churg Strauss syndrome (CSS) with poor prognosis factor(s): a prospective, randomized, multicenter trial comparing corticosteroids (CS) and 6 vs 12 cyclophosphamide [abstract]. 11th International Vasculitis & ANCA Workshop; 2003 Oct 2‐5; Prague, Czech Republic. 2003:43. [CENTRAL: CN‐00461457]
RATTRAP 2015 {published data only}
    1. Guillevin L. RATTRAP: Infliximab versus rituximab in systemic necrotizing vasculitides. www.clinicaltrials.gov/ct2/show/NCT00307593 (first received 28 March 2006).

References to ongoing studies

ADVOCATE 2019 {published data only}
    1. Merkel P, Jayne D, Harigai M, Schall T, Bekker P, Potarca A, et al. A randomized phase 3 trial evaluating the safety and efficacy of avacopan in patients with new or relapsing ANCA‐associated vasculitis [abstract]. Rheumatology 2019;58(Suppl 2):na. [EMBASE: 628291607]
ALEVIATE 2018 {published data only}
    1. Gopaluni S, Smith RM, Goymer D, Broadhurst E, Mcclure ME, Cahill HC, et al. Alemtuzumab for relapsing and refractory primary systemic vasculitis: a trial of efficacy and safety (ALEVIATE) [abstract no: TH‐PO1160]. Journal of the American Society of Nephrology 2018;29(Abstract Suppl):B8.
CANVAS 2016 {published data only}
    1. Chanouzas D, Dyall L, Dale J, Moss P, Morgan M, Harper L. CD4+CD28‐ T‐cell expansions in ANCA‐associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial [abstract no: 58]. Lancet 2015;385 Suppl 1:S30. [MEDLINE: ] - PubMed
    1. Chanouzas D, Dyall L, Dale J, Moss P, Morgan MD, Harper L. CD4+CD28‐ T‐cell expansions in ANCA‐associated vasculitis and association with arterial stiffness [abstract no: P51]. Nephron 2015;129(Suppl 2):135. - PubMed
    1. Chanouzas D, Dyall L, Nightingale P, Ferro C, Moss P, Morgan MD, et al. Valaciclovir to prevent cytomegalovirus mediated adverse modulation of the immune system in ANCA‐associated vasculitis (CANVAS): study protocol for a randomised controlled trial. Trials [Electronic Resource] 2016;17(1):338. [MEDLINE: ] - PMC - PubMed
    1. Chanouzas D, Sagmeister M, Dyall L, Ferro C, Moss P, Morgan MD, et al. Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANca Associated VASculitis (CANVAS): results of a randomised controlled clinical trial [abstract no: TH‐PO816]. Journal of the American Society of Nephrology 2016;27(Abstract Suppl):282A. - PMC - PubMed
    1. Chanouzas D, Sagmeister M, Dyall L, Nightingale P, Ferro C, Moss P, et al. Role of cytomegalovirus in the expansion of CD4+CD28‐T cells in patients with ANCA‐associated vasculitis: A proof‐of‐concept, randomised controlled trial [abstract]. Lancet 2017;389(Suppl 1):S17. [EMBASE: 618809848]
COMBIVAS 2019 {published data only}
    1. McClure M, Gopaluni S, Wason J, Rosen AN, Henderson R, Salama A, et al. A randomised, double‐blind, controlled, mechanistic study of rituximab and belimumab combination therapy in pr3 ANCA‐associated vasculitis (COMBIVAS): study protocol [abstract]. Rheumatology 2019;58(Suppl 2):na. [EMBASE: 628291554]
MAINRITSAN 3 2015 {published data only}
    1. Guillevin L. Comparison between a long term and a conventional maintenance treatment with rituximab (MAINRITSAN3). www.clinicaltrials.gov/ct2/show/NCT02433522 (first received 5 May 2015).
MUPIBAC 2004 {published data only}
    1. Buhaescu I. Actualities in the treatment of systemic vasculitis. BANTAO Journal 2004;2(2):4‐9. [CENTRAL: CN‐01658416]
NCT03323476 {published data only}
    1. Couvrat‐Desvergnes G. Maintaining or stopping immunosuppressive therapy in patients with ANCA vasculitis and end‐stage renal disease (MASTER‐ANCA). www.clinicaltrials.gov/show/NCT03323476 (first received 27 October 2017).
RITAZAREM 2013 {published data only}
    1. Gopaluni S, Smith RM, Lewin M, McAlear CA, Mynard K, Jones RB, et al. Rituximab versus azathioprine as therapy for maintenance of remission for anti‐neutrophil cytoplasm antibody‐associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials [Electronic Resource] 2017;18(1):112. [MEDLINE: ] - PMC - PubMed
    1. Jayne D, Smith R, Merkel P. An international, open‐label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA‐associated vasculitis (RITAZAREM) [abstract no: P205]. Press Medicale 2013;42(4 Pt 2):768. [EMBASE: 71944013]
    1. Jayne DR, Smith RM, Merkel PA. RITAZAREM: an international, open label, randomized, controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA‐associated vasculitis [abstract no: SA‐PO307]. Journal of the American Society of Nephrology 2012;23(Abstracts):707A. [CENTRAL: CN‐01912286]
    1. Smith R, Jones R, Speckes U, McAlear CA, Mynard K, Bond S, et al. Rituximab as re‐induction therapy in relapsing ANCA‐associated vasculitis [abstract no: 18L]. Arthritis & Rheumatology 2017;69(Suppl 10):na.
    1. Smith R, Lewin M, Jones R, Merkel P, Jayne D. RITAZAREM: an international, open label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA‐associated vasculitis [abstract]. Nephrology Dialysis Transplantation 2013;28(Suppl 1):i180‐1. [EMBASE: 71075527]
Tuin 2019 {published data only}
    1. Tuin J, Stassen PM, Bogdan DI, Broekroelofs J, Paassen P, Cohen Tervaert JW, et al. Mycophenolate mofetil versus cyclophosphamide for the induction of remission in nonlife‐threatening relapses of antineutrophil cytoplasmic antibody‐associated vasculitis: randomized, controlled trial. Clinical Journal of the American Society of Nephrology: CJASN 2019;14(7):1021‐8. [MEDLINE: ] - PMC - PubMed
    1. Tuin J, Stassen PM, Bogdan DI, Tervaert J, Sanders J, Stegeman CA. Mycophenolate mofetil versus cyclophosphamide for the induction of remission in non‐life‐threatening relapses of PR3 and MPOANCA associated vasculitis [abstract]. Rheumatology 2017;56(Suppl 3):iii16. [EMBASE: 619334519]

Additional references

Bolton 1989
    1. Bolton WK, Sturgill BC. Methylprednisolone therapy for acute crescentic rapidly progressive glomerulonephritis. American Journal of Nephrology 1989;9(5):368‐75. [MEDLINE: ] - PubMed
Bosch 2007
    1. Bosch X, Guilabert A, Espinosa G, Miropeix E. Treatment of antineutrophil cytoplasmic antibody‐associated vasculitis. JAMA 2007;298(6):655‐69. [MEDLINE: ] - PubMed
de Groot 2001
    1. Groot K, Adu D, Savage CO, EUVAS (European vasculitis study group). The value of pulse cyclophosphamide in ANCA‐associated vasculitis: meta‐analysis and critical review. Nephrology Dialysis Transplantation 2001;16(10):2018‐27. [MEDLINE: ] - PubMed
Fauci 1973
    1. Fauci AS, Wolff SM. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine 1973;52(6):535‐61. [MEDLINE: ] - PubMed
GRADE 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6. [MEDLINE: ] - PMC - PubMed
GRADE 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [MEDLINE: ] - PubMed
Harper 2011
    1. Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA‐associated vasculitis: long‐term follow‐up. Annals of the Rheumatic Diseases 2011;71(6):955‐60. [MEDLINE: ] - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [MEDLINE: ] - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Jayne 2000a
    1. Jayne DR, Chapel H, Adu D, Misbah S, O'Donoghue D, Scott D, et al. Intravenous immunoglobulin for ANCA‐associated systemic vasculitis with persistent disease activity. Qjm 2000;93(7):433‐9. [MEDLINE: ] - PubMed
Jennette 2003
    1. Jennette JC, Falk RJ. Renal and systemic vasculitis. In: Johnson RJ, Feehally J editor(s). Comprehensive clinical nephrology. 2nd Edition. Edinburgh: Mosby, 2003:341‐57. [ISBN 0723432589]
Jennette 2008
    1. Jennette JC, Falk RJ. New insight into the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies. Current Opinion in Rheumatology 2008;20(1):55‐60. [MEDLINE: ] - PubMed
Jennette 2013
    1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis & Rheumatism 2013;65(1):1‐11. [MEDLINE: ] - PubMed
KDIGO 2012
    1. Chapter 13: Pauci‐immune focal and segmental necrotizing glomerulonephritis. Kidney International Supplements 2012;2(2):233‐9. [MEDLINE: ] - PMC - PubMed
Kerr 2001
    1. Kerr PG, Chadban SJ, Atkins RC. Is there a role for plasma exchange in rapidly progressive glomerulonephritis?. Nephrology 2001;6(3):141‐3. [EMBASE: 2001231297]
Lapraik 2007
    1. Lapraik C, Watts R, Bacon P, Carruthers D, Chakravarty K, D'Cruz D, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology 2007;46(10):1615‐6. [MEDLINE: ] - PubMed
Levey 1994
    1. Levey JB, Winearls CG. Rapidly progressive glomerulonephritis: what should be first‐line therapy?. Nephron 1994;67(4):402‐7. [MEDLINE: ] - PubMed
Little 2010
    1. Little MA, Nightingale P, Verburgh CA, Hauser T, Groot K, Savage C, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Annals of the Rheumatic Diseases 2010;69(6):1036‐43. [MEDLINE: ] - PubMed
Lockwood 1976
    1. Lockwood CM, Rees AJ, Pearson TA, Evans DJ, Peters DK, Wilson CB. Immunosuppression and plasma exchange in the treatment of Goodpasture's syndrome. Lancet 1976;1(7962):711‐5. [MEDLINE: ] - PubMed
Lyons 2012
    1. Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, et al. Genetically distinct subsets within ANCA‐associated vasculitis. New England Journal of Medicine 2012;367(3):214‐23. [MEDLINE: ] - PMC - PubMed
Menahem 2008
    1. Menahem S, Hiremagalur B, Mudge D, Toussaint N, Walters G, Caring for Australians with Renal Impairment (CARI). The CARI guidelines. Induction and maintenance therapy in ANCA‐associated systemic vasculitis. Nephrology 2008;13 Suppl 2:S24‐36. [MEDLINE: ] - PubMed
Mukhtyar 2009
    1. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Annals of the Rheumatic Diseases 2009;68(3):310‐7. [MEDLINE: ] - PubMed
Nowack 1997
    1. Nowack, R, Birck R, Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy. Lancet 1997;349(9054):774. [MEDLINE: ] - PubMed
Phillip 2008
    1. Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clinical & Experimental Rheumatology 2008;26(5 Suppl 51):S94‐104. [MEDLINE: ] - PubMed
Rondeau 1989
    1. Rondeau E, Levy M, Dosquet P, Ruedin P, Mougenot B, Kanfer A, et al. Plasma exchange and immunosuppression for rapidly progressive glomerulonephritis: prognosis and complications. Nephrology Dialysis Transplantation 1989;4(3):196‐200. [MEDLINE: ] - PubMed
Savage 1997
    1. Savage CO, Harper L, Adu D. Primary systemic vasculitis. Lancet 1997;349(9051):553‐8. [MEDLINE: ] - PubMed
Schunemann 2011a
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and 'Summary of findings' tables. In: Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Schunemann 2011b
    1. Schünemann HJ, Oxman AD, Higgins JP, Deeks JJ, Glasziou P, Guyatt GH. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Seo 2004
    1. Seo P, Stone JH. The antineutrophil cytoplasmic antibody‐associated vasculitides. American Journal of Medicine 2004;117(1):39‐50. [MEDLINE: ] - PubMed
Tervaert 2001
    1. Tervaert JW, Stegeman CA, Kallenberg CG. Novel therapies for anti‐neutrophil cytoplasmic antibody‐associated vasculitis. Current Opinion in Nephrology & Hypertension 2001;10(2):211‐7. [MEDLINE: ] - PubMed
Walsh 2011
    1. Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta‐analysis. American Journal of Kidney Diseases 2011;57(4):566‐74. [MEDLINE: ] - PMC - PubMed

References to other published versions of this review

Walters 2001
    1. Walters G, Willis N, Craig JC, Kerr P. Treatment for renal vasculitis and Goodpasture's disease in adults. Cochrane Database of Systematic Reviews 2001, Issue 3. [DOI: 10.1002/14651858.CD003232] - DOI
Walters 2008
    1. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD003232.pub2] - DOI - PubMed
Walters 2010
    1. Interventions for renal vasculitis in adults. A systematic review. Walters GD, Willis NS, Craig JC. BMC Nephrology 2010;11:12. [MEDLINE: ] - PMC - PubMed
Walters 2015
    1. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD003232.pub3] - DOI - PubMed

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