New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

被引：13

作者：

Toboso, Inmaculada ^{[1
]}

Tejeda-Velarde, Amalia ^{[1
]}

Alvarez-Lafuente, Roberto ^{[2
]}

Arroyo, Rafael ^{[3
]}

Hegen, Harald ^{[4
]}

Deisenhammer, Florian ^{[4
]}

Sainz de la Maza, Susana ^{[5
]}

Alvarez-Cermeno, Jose C. ^{[5
]}

Izquierdo, Guillermo ^{[6
]}

Paramo, Dolores ^{[6
]}

Oliva, Pedro ^{[7
]}

Casanova, Bonaventura ^{[8
]}

Aguera-Morales, Eduardo ^{[9
]}

Franciotta, Diego ^{[10
]}

Gastaldi, Matteo ^{[10
]}

Fernandez, Oscar ^{[11
]}

Urbaneja, Patricia ^{[11
]}

Garcia-Dominguez, Jose M. ^{[12
]}

Romero, Fernando ^{[12
]}

Laroni, Alicia ^{[13
]}

Uccelli, Antonio ^{[13
]}

Perez-Sempere, Angel ^{[14
]}

Saiz, Albert ^{[15
,16
]}

Blanco, Yolanda ^{[15
,16
]}

Galimberti, Daniela ^{[17
]}

Scarpini, Elio ^{[17
]}

Espejo, Carmen ^{[18
]}

Montalban, Xavier ^{[18
]}

Rasche, Ludwig ^{[19
,20
,21
]}

Paul, Friedemann ^{[19
,20
,21
,22
]}

Gonzalez, Ines ^{[23
]}

Alvarez, Elena ^{[23
]}

Ramo, Cristina ^{[24
]}

Caminero, Ana B. ^{[25
]}

Aladro, Yolanda ^{[26
]}

Calles, Carmen ^{[27
]}

Eguia, Pablo ^{[28
]}

Belenguer-Benavides, Antonio ^{[29
]}

Ramio-Torrenta, Lluis ^{[30
]}

Quintana, Ester ^{[30
]}

Martinez-Rodriguez, Jose E. ^{[31
]}

Oterino, Agustin ^{[32
]}

Lopez de Silanes, Carlos ^{[33
]}

Casanova, Luis I. ^{[33
]}

Landete, Lamberto ^{[34
]}

Frederiksen, Jette ^{[35
]}

Bsteh, Gabriel ^{[4
]}

Mulero, Patricia ^{[18
]}

Comabella, Manuel ^{[18
]}

Hernandez, Miguel A. ^{[36
]}

机构：

[1] Hosp Univ Ramon y Cajal, Immunol Dept, Madrid, Spain

[2] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IDISSC, Madrid, Spain

[3] Hosp Univ Quiron Salud, Dept Neurol, Madrid, Spain

[4] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[5] Hosp Univ Ramon y Cajal, Neurol Dept, Madrid, Spain

[6] Hosp Univ Virgen Macarena, Neurol Dept, Seville, Spain

[7] Hosp Univ Cent Asturias, Neurol Dept, Oviedo, Spain

[8] Hosp Univ La Fe, Neurol Dept, Valencia, Spain

[9] Hosp Univ Reina Sofia, Neurol Dept, Cordoba, Spain

[10] Mondino Fdn, Ist Recovero & Cura Carattere Sci IRCCS, Pavia, Italy

[11] Hosp Reg Univ, Neurol Dept, Malaga, Spain

[12] Hosp Gen Univ Gregorio Maranon, Neurol Dept, Madrid, Spain

[13] Univ Genoa, Osped Policlin San Martino, Genoa, Italy

[14] Hosp Gen Univ Alicante, Neurol Dept, Alicante, Spain

[15] Univ Barcelona, Hosp Clin Barcelona, Neurol Serv, Barcelona, Spain

[16] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[17] Univ Milan, Ctr Dino Ferrari, Ist Recovero & Cura Carattere Sci IRCCS, Osped Policlin,Fdn Ca Granda, Milan, Italy

[18] Univ Autonoma Barcelona, Ctr Esclerosi Multiple Catalunya, Serv Neurol Neuroimmunol, Hosp Univ Vall dHebron,Vall dHebron Inst Recerca, Barcelona, Spain

[19] Charite Univ Med Berlin, Dept Neurol, NeuroCure Clin Res Ctr, Berlin, Germany

[20] Free Univ Berlin, Berlin, Germany

[21] Humboldt Univ, Berlin Inst Hlth, Berlin, Germany

[22] Charite Univ Med Berlin, Max Delbruck Ctr Mol Med, Expt & Clin Res Ctr, Berlin, Germany

[23] Hosp Alvaro Cunqueiro, Neurol Dept, Vigo, Spain

[24] Hosp Badalona Germans Trias & Pujol, Neurol Dept, Badalona, Spain

[25] Hosp Nuestra Senora Sonsoles, Neurol Dept, Avila, Spain

[26] Hosp Univ Getafe, Neurol Dept, Getafe, Spain

[27] Hosp Univ Son Espases, Neurol Dept, Palma De Mallorca, Spain

[28] Hosp Doctor Jose Molina Orosa, Neurol Dept, Arrecife, Spain

[29] Hosp Gen Univ Castellon, Neurol Dept, Castellon de La Plana, Spain

[30] Hosp Univ Doctor Josep Trueta, Neurol Dept, Girona, Spain

[31] Hosp del Mar, Neurol Dept, Barcelona, Spain

[32] Hosp Univ Marques Valdecilla, Neurol Dept, Santander, Spain

[33] Hosp Univ Torrejon, Neurol Dept, Torrejon De Ardoz, Spain

[34] Hosp Univ Dr Peset, Neurol Dept, Valencia, Spain

[35] Univ Copenhagen, Glostrup Hosp, Copenhagen, Denmark

[36] Hosp Univ Nuestra Senora Candelaria, Neurol Dept, Tenerife, Spain

[37] Hosp Clin Santiago, Neurol Dept, Santiago De Compostela, Spain

[38] Hosp Bierzo, Neurol Dept, Ponferrada, Spain

[39] Complejo Hosp Navarra, Neurol Dept, Pamplona, Spain

[40] Hosp Clin Malaga, Neurol Dept, Malaga, Spain

[41] Hosp Puerta Hierro, Neurol Dept, Madrid, Spain

[42] Hosp Gen Elche, Neurol Dept, Elche, Spain

[43] Hosp Univ Ramon y Cajal, Inst Ramon y Cajal Invest Sanitaria IRYCIS, Biostat Unit, Madrid, Spain

来源：

FRONTIERS IN NEUROLOGY | 2020年 / 11卷

关键词：

multiple sclerosis; demyelinating diseases; biomarkers; natalizumab; progressive multifocal leucoencephalopathy; disease modifying treatments; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; MULTIPLE-SCLEROSIS; ALEMTUZUMAB; DISEASE; BIOMARKER; TRIAL;

D O I：

10.3389/fneur.2020.579438

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

引用

页数：11

共 28 条

[1] Progressive multifocal leukoencephalopathy in patients with multiple sclerosis [J].

Baldwin, Kelly J. ;

Hogg, Jeffery P. .

CURRENT OPINION IN NEUROLOGY, 2013, 26 (03) :318-323

[2] Progressive multifocal leukoencephalopathy after fingolimod treatment [J].

Berger, Joseph R. ;

Cree, Bruce A. ;

Greenberg, Benjamin ;

Hemmer, Bernhard ;

Ward, Brian J. ;

Dong, Victor M. ;

Merschhemke, Martin .

NEUROLOGY, 2018, 90 (20) :E1815-E1821

[3]

Berger JR, 2016, J NEUROVIROL, V22, P533, DOI 10.1007/s13365-016-0427-6

[4] Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy [J].

Bloomgren, Gary ;

Richman, Sandra ;

Hotermans, Christophe ;

Subramanyam, Meena ;

Goelz, Susan ;

Natarajan, Amy ;

Lee, Sophia ;

Plavina, Tatiana ;

Scanlon, James V. ;

Sandrock, Alfred ;

Bozic, Carmen .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (20) :1870-1880

[5] Statistical analysis of PML incidences of natalizumab-treated patients from 2009 to 2016: outcomes after introduction of the Stratify JCVA® DxSelect™ antibody assay [J].

Campagnolo, Denise ;

Dong, Qunming ;

Lee, Lily ;

Ho, Pei-Ran ;

Amarante, Diogo ;

Koendgen, Harold .

JOURNAL OF NEUROVIROLOGY, 2016, 22 (06) :880-881

[6]

Coles AJ, 2008, NEW ENGL J MED, V359, P1786, DOI 10.1056/NEJMoa0802670

[7]

Coles AJ, 2017, NEUROLOGY, V89, P1117, DOI 10.1212/WNL.0000000000004354

[8] Alemtuzumab-Related Thyroid Dysfunction in a Phase 2 Trial of Patients With Relapsing-Remitting Multiple Sclerosis [J].

Daniels, Gilbert H. ;

Vladic, Anton ;

Brinar, Vesna ;

Zavalishin, Igor ;

Valente, William ;

Oyuela, Pedro ;

Palmer, Jeffrey ;

Margolin, David H. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (01) :80-89

[9] Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010 [J].

Faissner, Simon ;

Gold, Ralf .

CNS DRUGS, 2018, 32 (03) :269-287

[10] Immunosenescence: the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis [J].

Grebenciucova, Elena ;

Berger, Joseph R. .

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2017, 17 (08)

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