Comparative Effectiveness of Natalizumab Versus Anti-CD20 in Highly Active Relapsing-Remitting Multiple Sclerosis After Fingolimod Withdrawal

被引：8

作者：

Rollot, Fabien ^{[1
,2
,3
,4
,5
]}

Couturier, Justine ^{[6
]}

Casey, Romain ^{[1
,2
,3
,4
,5
]}

Wiertlewski, Sandrine ^{[6
,7
]}

Debouverie, Marc ^{[8
]}

Pelletier, Jean ^{[9
]}

De Seze, Jerome ^{[10
,11
]}

Labauge, Pierre ^{[12
]}

Ruet, Aurelie ^{[13
,14
]}

Thouvenot, Eric ^{[15
,16
]}

Ciron, Jonathan ^{[17
,18
]}

Berger, Eric ^{[19
]}

Gout, Olivier ^{[20
]}

Clavelou, Pierre ^{[21
]}

Stankoff, Bruno ^{[22
]}

Casez, Olivier ^{[23
]}

Bourre, Bertrand ^{[24
]}

Zephir, Helene ^{[25
]}

Moreau, Thibault ^{[26
]}

Lebrun-Frenay, Christine ^{[27
]}

Maillart, Elisabeth ^{[28
]}

Edan, Gilles ^{[29
]}

Neau, Jean-Philippe ^{[30
]}

Montcuquet, Alexis ^{[31
]}

Cabre, Philippe ^{[32
]}

Camdessanche, Jean-Philippe ^{[33
]}

Defer, Gilles ^{[34
]}

Ben Nasr, Haifa ^{[35
]}

Maurousset, Aude ^{[36
]}

Hankiewicz, Karolina ^{[37
]}

Pottier, Corinne ^{[38
]}

Leray, Emmanuelle ^{[39
,40
]}

Vukusic, Sandra ^{[1
,2
,3
,4
,5
]}

Laplaud, David-Axel ^{[6
,7
]}

机构：

[1] Univ Lyon, Univ Claude Bernard, Lyon 1, Lyon, France

[2] Hosp Civils Lyon, Serv Neurol, Hop Neurol Pierre Wertheimer, Sclerose Plaques Pathol Myeline & Neuroinflammat, Bron, France

[3] Ctr Rech Neurosci Lyon, Observ Francais Sclerose Plaques, INSERM 1028, Lyon, France

[4] CNRS UMR 5292, Lyon, France

[5] State Approved Fdn, EUGENE DEVIC EDMUS Fdn Multiple Sclerosis, Bron, France

[6] CHU Nantes, Serv Neurol, Nantes, France

[7] CRTI INSERM UMR U1064, INSERM, CIC 0004, Nantes, France

[8] Univ Lorraine, Serv Neurol, Ctr Hosp Reg & Univ Nancy, 4360 APEMAC, Vandoeuvre Les Nancy, EA, France

[9] Aix Marseille Univ, Hop La Timone, AP HM, Pole Neurosci Clin,Serv Neurol,CEMEREM, F-13005 Marseille, France

[10] CHU Strasbourg, Serv Neurol, INSERM 1434, Strasbourg, France

[11] CHU Strasbourg, Ctr Invest Clin, Strasbourg, France

[12] CHU Montpellier, Serv Neurol, Montpellier, France

[13] CHU Bordeaux, Serv Neurol, Bordeaux, France

[14] Univ Bordeaux, Neuroctr Magendie, U1215, INSERM, Bordeaux, France

[15] CHU Nimes, Serv Neurol, Nimes, France

[16] Univ Montpellier, Inst Genom Fonct, INSERM, CNRS, Montpellier, France

[17] CHU Toulouse, CRC SEP, Hop Pierre Paul Riquet, Serv Neurol, Toulouse, France

[18] Univ Toulouse III, Inst Toulousain Malad Infect & Inflammatoires Inf, INSERM UMR 1291, CNRS UMR 5051, Toulouse, France

[19] Serv Neurol, CHU Besancon, Besancon, France

[20] Hop Fdn A Rothschild, Serv Neurol, Paris, France

[21] CHU Clermont Ferrand, Serv Neurol, Clermont Ferrand, France

[22] CHU St Antoine, Serv Neurol, Paris, France

[23] CHU Grenoble, Serv Neurol, Grenoble, France

[24] CHU Rouen, Serv Neurol, Rouen, France

[25] Univ Lille, Pole Neurosci & Appareil Locomoteur, CRC SEP, Hop Roger Salengro,Inserm U1172, Lille, France

[26] CHU Dijon, Serv Neurol, Dijon, France

[27] Univ Nice Cote Azur, Serv Neurol, Neurol Pasteur 2, CHU Nice,UR2CA URRIS, Nice, France

[28] Hop La Pitie Salpetriere, AP HP, Dept Neurol, Paris, France

[29] CHU Pontchaillou, Serv Neurol, Rennes, France

[30] CHU La Miletrie, Serv Neurol, Poitiers, France

[31] CHU Limoges, Serv Neurol, Limoges, France

[32] CHU Ft France, Serv Neurol, Fort De France, Martinique, France

[33] CHU St Etienne, Hop Nord, Serv Neurol, St Etienne, France

[34] Univ Normandie, Ctr Expert SEP, Serv Neurol, CHU Caen, Caen, France

[35] Hop Sud Francilien, Serv Neurol, Corbeil Essonnes, France

[36] CHU Bretonneau, Serv Neurol, Tours, France

[37] CH St Denis, Serv Neurol, St Denis, France

[38] Hop Rene Dubos, Serv Neurol, Pontoise, France

[39] Univ Rennes, REPERES EA, EHESP, F-7449 Rennes, France

[40] CHU Rennes, CIC P 1414, Rennes, France

来源：

NEUROTHERAPEUTICS | 2022年 / 19卷 / 02期

关键词：

Multiple sclerosis; Fingolimod; Natalizumab; Anti-CD20; Therapeutics; Effectiveness; Flexible model; PLACEBO-CONTROLLED TRIAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ORAL FINGOLIMOD; RITUXIMAB; OCRELIZUMAB; INTERFERON;

D O I：

10.1007/s13311-022-01202-1

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing-remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions.

引用

页码：476 / 490

页数：15

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