Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials

被引：29

作者：

Delestre, Florence ^{[1
,2
]}

Charles, Pierre ^{[2
,3
]}

Karras, Alexandre ^{[2
,4
]}

Pagnoux, Christian ^{[5
,6
]}

Neel, Antoine ^{[7
]}

Cohen, Pascal ^{[1
]}

Aumaitre, Olivier ^{[8
]}

Faguer, Stanislas ^{[9
]}

Gobert, Pierre ^{[10
]}

Maurier, Francois ^{[11
]}

Samson, Maxime ^{[12
]}

Godmer, Pascal ^{[13
]}

Bonnotte, Bernard ^{[12
]}

Cottin, Vincent ^{[14
]}

Hanrotel-Saliou, Catherine ^{[15
]}

Le Gallou, Thomas ^{[16
]}

Carron, Pierre-Louis ^{[17
]}

Desmurs-Clavel, Helene ^{[18
]}

Direz, Guillaume ^{[19
]}

Jourde-Chiche, Noemie ^{[20
]}

Lifermann, Francois ^{[21
]}

Martin-Silva, Nicolas ^{[22
]}

Pugnet, Gregory ^{[23
]}

Quemeneur, Thomas ^{[24
]}

Matignon, Marie ^{[25
]}

Benhamou, Ygal ^{[26
]}

Daugas, Eric ^{[27
]}

Lazaro, Estibaliz ^{[28
]}

Limal, Nicolas ^{[29
]}

Ducret, Maize ^{[30
]}

Huart, Antoine ^{[31
]}

Viallard, Jean-Francois ^{[28
]}

Hachulla, Eric ^{[32
]}

Perrodeau, Elodie ^{[33
]}

Puechal, Xavier ^{[1
,2
]}

Guillevin, Loic ^{[1
,2
]}

Porcher, Raphael ^{[2
,33
]}

Terrier, Benjamin ^{[1
,2
]}

机构：

[1] Hosp Cochin, Natl Reference Ctr Rare Syst Autoimmune Dis, AP HP Ctr, Dept Internal Med, Paris, France

[2] Univ Paris Cite, Paris, France

[3] Inst Mutualiste Montsouris, Dept Internal Med, Paris, France

[4] Hop Europeen Georges Pompidou, AP HP, Dept Nephrol, Paris, France

[5] Univ Toronto, Toronto, ON, Canada

[6] Mt Sinai Hosp, Vasculitis Clin, Toronto, ON, Canada

[7] Ctr Hosp Univ Nantes, Dept Internal Med, Nantes, France

[8] Hop Gabriel Montpied, Dept Internal Med, Clermont Ferrand, France

[9] Ctr Hosp Univ Toulouse, Dept Nephrol & Transplantat Organes, Toulouse, France

[10] Hop Gen Henri Duffaut, Dept Med, Avignon, France

[11] Hop Prives Metz, Dept Internal Med, Metz, France

[12] Ctr Hosp Univ Dijon, Dept Med Interne & Immunol Clin, Dijon, France

[13] Ctr Hosp Bretagne Atlant Vannes, Dept Hematol Immunol, Vannes, France

[14] Louis Pradel Hosp, Dept Resp Med, Natl Coordinating Reference Ctr Rare Pulm Dis, Lyon, France

[15] Ctr Hosp Reg Univ Brest, Hop Cavale Blanche, Dept Nephrol, Brest, France

[16] Ctr Hosp Univ Rennes, Dept Internal Med, Rennes, France

[17] Ctr Hosp Univ Grenoble Alpes, Dept Nephrol, Grenoble, France

[18] Hop Edouard Herriot, Dept Internal Med, Lyon, France

[19] Le Mans Gen Hosp, Rheumatol Dept, Le Mans, France

[20] Aix Marseille Univ, Hop La Conception, Ctr Nephrol & Transplantat Renale, Marseille, France

[21] Ctr Hosp Dax, Dept Internal Med, Dax, France

[22] Ctr Hosp Univ Caen, Dept Internal Med, Caen, France

[23] Ctr Hosp Univ Toulouse, Dept Internal Med, Toulouse, France

[24] Ctr Hosp Valenciennes, Dept Nephrol & Med Interne, Valenciennes, France

[25] Hop Univ Henri Mondor, Nephrol & Renal Transplantat Dept, Creteil, France

[26] Ctr Hosp Univ Charles Nicolle, Dept Internal Med, Rouen, France

[27] Hop Bichat Claude Bernard, Dept Nephrol, Paris, France

[28] Bordeaux Univ Hosp, Dept Internal Med, Pessac, France

[29] Hop Henri Mondor, Dept Internal Med, Creteil, France

[30] Annecy Hosp, Dept Nephrol, Annecy, France

[31] Hosp Rangueil, Dept Nephrol, Toulouse, France

[32] Ctr Hosp Univ Lille, Ctr Reference Malad Syst & Autoimmunes Rares Nord, Dept Med Interne & Immunol Clin, Lille, France

[33] Sorbonne Paris Cite, Ctr Res Epidemiol & Stat, Paris, France

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2024年 / 83卷 / 02期

关键词：

Rituximab; Systemic vasculitis; Autoimmune Diseases; CYCLOPHOSPHAMIDE;

D O I：

10.1136/ard-2023-224623

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectiveTo compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively).MethodsThe Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84.Results277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25).ConclusionsAccording to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

引用

页码：233 / 241

页数：9

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