The incidence and significance of anti-natalizumab antibodies -: Results from AFFIRM and SENTINEL

被引：248

作者：

Calabresi, P. A. ^{[1
]}

Giovannoni, G. ^{[74
]}

Confavreux, C. ^{[118
]}

Galetta, S. L.

Havrdova, E. ^{[25
]}

Hutchinson, M. ^{[49
]}

Kappos, L. ^{[71
,148
]}

Miller, D. H.

O'Connor, P. W.

Phillips, J. T. ^{[93
,197
]}

Polman, C. H. ^{[142
]}

Radue, E. -W.

Rudick, R. A.

Stuart, W. H.

Lublin, F. D.

Wajgt, A. ^{[61
]}

Weinstock-Guttman, B. ^{[159
]}

Wynn, D. R.

Lynn, F.

Panzara, M. A.

Macdonell, R. ^{[1
]}

Hughes, A. ^{[1
]}

Taylor, I. ^{[1
]}

Lee, Y. C. ^{[1
]}

Ma, H. ^{[1
]}

King, J. ^{[2
]}

Kilpatrick, T. ^{[2
]}

Butzkueven, H. ^{[2
]}

Marriott, M. ^{[2
]}

Pollard, J. ^{[3
]}

Spring, P. ^{[3
]}

Spies, J. ^{[3
]}

Barnett, M. ^{[3
]}

Dehaene, I. ^{[4
]}

Vanopdenbosch, L. ^{[4
]}

D'Hooghe, M. ^{[4
,7
]}

Van Zandijcke, M. ^{[4
]}

Derijck, O. ^{[4
]}

Seeldrayers, P. ^{[5
]}

Jacquy, J. ^{[5
]}

Piette, T. ^{[5
]}

De Cock, C. ^{[5
]}

Medaer, R. ^{[6
]}

Soors, P. ^{[6
]}

Vanroose, E. ^{[6
]}

Vanderhoven, L. ^{[6
]}

Nagels, G. ^{[7
]}

Dubois, B. ^{[7
]}

Deville, M. -C. ^{[7
]}

D'Haene, R. ^{[7
]}

机构：

[1] Austin Hlth, Melbourne, Vic, Australia

[2] Royal Melbourne Hosp, Melbourne, Vic, Australia

[3] Univ Sydney, Sydney, NSW, Australia

[4] Algemeen Ziekenhuis St Jan, Brugge, Belgium

[5] CHU De Charleroi, Charleroi, Belgium

[6] Limburgs Univ Ctr, Diepenbeek, Belgium

[7] Natl MS Centrum, Melsbroek, Belgium

[8] CHVO Hosp Hull, Gatineau, PQ, Canada

[9] QEII, Dalhousie MS Res Unit, Halifax, NS, Canada

[10] SCO Elisabeth Bruyere Hlth Ctr, Ottawa, ON, Canada

[11] Hlth Serv Ctr, Winnipeg, MB, Canada

[12] Hosp Charles Lemoyne, Greenfield Pk, PQ, Canada

[13] Kingston Gen Hosp, Kingston, ON, Canada

[14] St Michaels Hosp, Toronto, ON, Canada

[15] Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada

[16] UBC Hosp, Vancouver Coastal Hlth Author, Vancouver, BC, Canada

[17] Univ Campus London Hlth Sci Ctr, London, ON, Canada

[18] Fac Hosp Brno Bohunice, Brno, Czech Republic

[19] Fac Hosp Motol, Prague, Czech Republic

[20] Fac Hosp Hradec Kralove, Hradec Kralove, Czech Republic

[21] Fac Hosp Olomouc, Olomouc, Czech Republic

[22] Fac Hosp Ostrava Poruba, Ostrava, Czech Republic

[23] Fac Hosp Plzen, Plzen, Czech Republic

[24] Fac Hosp St Anne, Brno, Czech Republic

[25] Gen Teaching Hosp, Prague, Czech Republic

[26] Reg Hosp Pardubice, Pardubice, Czech Republic

[27] Rigshosp, Copenhagen, Denmark

[28] Helsingin Yliopistollinen Keskussairaala, Helsinki, Finland

[29] Tampere Univ Hosp, Tampere, Finland

[30] Hop Adultes Timone, Marseille, France

[31] Hop Pontchaillou, Rennes, France

[32] Hop Purpan, Toulouse, France

[33] Hop Univ, Strasbourg, France

[34] Klinikum Offenbach, Neurol Klin, Offenbach, Germany

[35] Ruhr Univ Bochum, St Josef Hosp, Neurol Klin, Bochum, Germany

[36] Univ Klinikum Hamburg Eppendorf, Hamburg, Germany

[37] Dist Gen Hosp G Gennimatas, Athens, Greece

[38] Pammakaristos Gen Hosp, Athens, Greece

[39] Jahn Ferenc Hosp, Budapest, Hungary

[40] Josa Andras Hosp, Nyiregyhaza, Hungary

[41] Kenezy Gyula Hosp, Debrecen, Hungary

[42] Natl Inst Psychiat & Neurol, Budapest, Hungary

[43] Petz Aladar County Hosp, Gyor, Hungary

[44] Semmelweis Univ, Budapest, Hungary

[45] St Imre Hosp, Budapest, Hungary

[46] Szent Gyorgy Hosp, Szekesfehervar, Hungary

[47] Univ Debrecen, Debrecen, Hungary

[48] Uzsoki Hosp, Budapest, Hungary

[49] Vincents Univ Hosp, Dublin, Ireland

[50] Amphia Ziekenhuis, Breda, Netherlands

来源：

NEUROLOGY | 2007年 / 69卷 / 14期

关键词：

D O I：

10.1212/01.wnl.0000277457.17420.b5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double- blind, placebo- controlled studies ( natalizumab safety and efficacy in relapsing remitting multiple sclerosis [ MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon beta- 1a [ INF beta 1a] in patients with relapsing remitting MS [ SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as " transiently positive" if they had detectable antibodies ( >= 0.5 mu g/ mL) at a single time point or " persistently positive" if they had antibodies at two or more time points >= 6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 ( 9%) of natalizumab- treated patients: Twenty ( 3%) were transiently positive and 37 ( 6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p <= 0.05), relapse rate ( p= 0.009), and MRI ( p <= 0.05) compared with antibody- negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusionrelated adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody- negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion- related adverse events should be considered for antibody testing.

引用

页码：1391 / 1403

页数：13

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[11] Bioequivalence and the immunogenicity of biopharmaceuticals [J].