Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition

被引：22

作者：

Goncalves, J. ^{[1
]}

Santos, M. ^{[1
]}

Acurcio, R. ^{[1
]}

Iria, I. ^{[1
,2
]}

Gouveia, L. ^{[1
]}

Matos Brito, P. ^{[1
]}

Catarina Cunha-Santos, A. ^{[1
]}

Barbas, A. ^{[3
,4
]}

Galvao, J. ^{[3
]}

Barbosa, I. ^{[3
]}

Aires da Silva, F. ^{[5
]}

Alcobia, A. ^{[6
]}

Cavaco, M. ^{[7
]}

Cardoso, M. ^{[1
]}

Delgado Alves, J. ^{[8
,9
]}

Carey, J. J. ^{[10
]}

Doerner, T. ^{[11
]}

Eurico Fonseca, J. ^{[7
,12
]}

Palmela, C. ^{[13
]}

Torres, J. ^{[13
]}

Lima Vieira, C. ^{[14
]}

Trabuco, D. ^{[14
]}

Fiorino, G. ^{[15
]}

Strik, A. ^{[16
]}

Yavzori, M. ^{[17
,18
]}

Rosa, I. ^{[19
]}

Correia, L. ^{[20
]}

Magro, F. ^{[21
]}

D'Haens, G. ^{[16
]}

Ben-Horin, S. ^{[17
,18
]}

Lakatos, P. L. ^{[22
]}

Danese, S. ^{[15
]}

机构：

[1] Univ Lisbon, Fac Farm, Res Inst Med iMed ULisboa, Lisbon, Portugal

[2] Univ Lisbon, INESC MN Inst Engn Sistemas & Comp Microsistemas, Lisbon, Portugal

[3] Inst Biol Expt & Tecnol, iBET, Oeiras, Portugal

[4] Bayer Portugal, Carnaxide, Portugal

[5] Univ Lisbon, CIISA, Fac Med Vet, Lisbon, Portugal

[6] HGO, EPE Av Torrado da Silva, Almada, Portugal

[7] Univ Lisbon, Inst Med Mol, Fac Med, Lisbon, Portugal

[8] CEDOC NOVA Med Sch, Lisbon, Portugal

[9] Fernando Fonseca Hosp, Immunomediated Syst Dis Unit UDIMS, Amadora, Portugal

[10] Galway Univ Hosp, Dept Rheumatol, Merlin Pk, Galway, Ireland

[11] Charite Univ Med Berlin, Dept Med Rheumatol & Clin Immunol, Berlin, Germany

[12] Hosp Santa Maria, Lisbon Acad Med Ctr, Rheumatol Dept, Ctr Hosp Lisboa Norte,EPE, Lisbon, Portugal

[13] Hosp Beatriz Angelo, Div Gastroenterol, Loures, Portugal

[14] CHBM, Unidade Gastroenterol, Barreiro, Portugal

[15] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[16] Acad Med Ctr, Amsterdam, Netherlands

[17] Tel Aviv Univ, Dept Gastroenterol, Sheba Med Ctr, Tel Aviv, Israel

[18] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[19] EPE, Portuguese Inst Oncol Lisbon Francisco Gentil, Lisbon, Portugal

[20] Univ Lisbon, Hosp Santa Maria, Dept Gastroenterol & Hepatol, Lisbon, Portugal

[21] Univ Porto, Gastroenterol Dept, Fac Med, Ctr Hosp Sao Joao, Porto, Portugal

[22] Semmelweis Univ, Dept Med 1, Budapest, Hungary

来源：

ALIMENTARY PHARMACOLOGY & THERAPEUTICS | 2018年 / 48卷 / 05期

关键词：

CROHNS-DISEASE; DOUBLE-BLIND; INNOVATOR INFLIXIMAB; MAINTENANCE THERAPY; ANTIBODY-RESPONSES; CLINICAL-RELEVANCE; BIOSIMILAR CT-P13; PARALLEL-GROUP; IMMUNOGENICITY; EFFICACY;

D O I：

10.1111/apt.14808

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Aim: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. Methods: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. Results: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P<0.001). Anti-CT-P13 sera of patients with IBD (n=32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naive individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. Conclusions: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.

引用

页码：507 / 522

页数：16

共 36 条

[1] Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays [J].