Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis

被引：49

作者：

Quistrebert, Jocelyn ^{[1
]}

Hassler, Signe ^{[1
]}

Bachelet, Delphine ^{[1
]}

Mbogning, Cyprien ^{[1
]}

Musters, Anne ^{[2
]}

Tak, Paul Peter ^{[2
,3
,4
,5
]}

Wijbrandts, Carla Ann ^{[2
,6
]}

Herenius, Marieke ^{[2
]}

Bergstra, Sytske Anne ^{[7
]}

Akdemir, Gulsah ^{[7
]}

Johannesson, Martina ^{[8
]}

Combe, Bernard ^{[9
]}

Fautrel, Bruno ^{[10
,11
]}

Chollet-Martin, Sylvie ^{[12
]}

Gleizes, Aude ^{[12
,13
]}

Donnellan, Naoimh ^{[14
]}

Deisenhammer, Florian ^{[15
]}

Davidson, Julie ^{[16
]}

Hincelin-Mery, Agnes ^{[17
]}

Donnes, Pierre ^{[18
]}

Fogdell-Hahn, Anna ^{[19
]}

De Vries, Niek ^{[2
]}

Huizinga, Tom ^{[7
]}

Abugessaisa, Imad ^{[20
]}

Saevarsdottir, Saedis ^{[8
]}

Hacein-Bey-Abina, Salima ^{[13
,21
]}

Pallardy, Marc ^{[12
]}

Broet, Philippe ^{[1
,22
,23
]}

Mariette, Xavier ^{[24
,25
]}

机构：

[1] Paris Saclay Univ, Paris Sud Univ, Fac Med, CESP,INSERM UMR 1018,UVSQ, Villejuif, France

[2] Univ Amsterdam, Acad Med Ctr, Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands

[3] GlaxoSmithKline, Stevenage, Herts, England

[4] Univ Cambridge, Cambridge, England

[5] Univ Ghent, Ghent, Belgium

[6] Med Ctr Slotervaart, Amsterdam, Netherlands

[7] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands

[8] Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden

[9] Univ Montpellier, Lapeyronie Hosp, Dept Rheumatol, Montpellier, France

[10] Hop La Pitie Salpetriere, AP HP, Dept Rheumatol, Paris, France

[11] UPMC, Pierre Louis Inst Epidemiol & Publ Hlth, GRC 08, Paris, France

[12] Paris Saclay Univ, Paris Sud Univ, Fac Pharm, INSERM UMR 996, Chatenay Malabry, France

[13] Le Kremlin Bicetre Hosp, Paris Sud Univ Hosp, AP HP, Clin Immunol Lab, Le Kremlin Bicetre, France

[14] IPSEN, Slough, Berks, England

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

[16] GlaxoSmithKline, Uxbridge, Middx, England

[17] Sanofi, Chilly Mazarin, France

[18] SciCross AB, Skovde, Sweden

[19] Karolinska Inst, Dept Clin Neurosci, Clin Neuroimmunol, Stockholm, Sweden

[20] Karolinska Inst, Dept Med Solna, Unit Computat Med, Stockholm, Sweden

[21] Paris Descartes Sorbonne Cite Univ, Fac Pharm, INSERM U1022, UTCBS,CNRS UMR 8258, Paris, France

[22] Hop Paul Brousse, Paris Sud Univ Hosp, AP HP, Villejuif, France

[23] CHU St Justine, Quebec City, PQ, Canada

[24] Paris Saclay Univ, Paris Sud Univ, Ctr Immunol Viral Infect & Autoimmune Dis, INSERM U1184, 63 Rue Gabriel Peri, F-94276 Le Kremlin Bicetre, France

[25] Le Kremlin Bicetre Hosp, Paris Sud Univ Hosp, AP HP, Dept Rheumatol, Le Kremlin Bicetre, France

来源：

SEMINARS IN ARTHRITIS AND RHEUMATISM | 2019年 / 48卷 / 06期

关键词：

Rheumatoid arthritis; Anti-drug antibodies; Anti-TNF treatment; Incidence; Risk factors; LONG-TERM TREATMENT; CLINICAL-RESPONSE; NEUTRALIZING ANTIBODIES; DISEASE-ACTIVITY; IMMUNOGENICITY; RECOMMENDATIONS; METHOTREXATE; ETANERCEPT; VALIDATION; INHIBITORS;

D O I：

10.1016/j.semarthrit.2018.10.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives: To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients. Methods: The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n =126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n=341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme-linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data. Results: ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2-20.2) and 0% (0-5.9) at 3 months, 17.6% (11.4-26.4) and 0% (0-25.9) at 6 months, 17.7% (12.6-37.5) and 34.1% (11.4-46.3) at 12 months, 50.0% (25.9-87.5) and 37.5% (25.9-77.4) at 15 months and 50.0% (25.9-87.5) and 66.7% (37.7-100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1-3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0-8.7; infliximab: HR 2.7, 95% CI 1.1-6.8), moderate disease activity (DAS28 3.2-5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3-33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2-6.3). Conclusions: The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：967 / 975

页数：9

共 58 条

[11] Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor α inhibitor infliximab [J].

Bendtzen, Klaus ;

Geborek, Pierre ;

Svenson, Morten ;

Larsson, Lotta ;

Kapetanovic, Meliha C. ;

Saxne, Tore .

ARTHRITIS AND RHEUMATISM, 2006, 54 (12) :3782-3789

[12] Immunogenicity of anti-TNF-α biotherapies: I. Individualized medicine based on immunopharmacological evidence [J].

Bendtzen, Klaus .

FRONTIERS IN IMMUNOLOGY, 2015, 6

[13] Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis [J].

Chen, Der-Yuan ;

Chen, Yi-Ming ;

Tsai, Wen-Chan ;

Tseng, Jui-Cheng ;

Chen, Yi-Hsing ;

Hsieh, Chia-Wei ;

Hung, Wei-Ting ;

Lan, Joung-Liang .

ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (03)

[14] Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance [J].

Collet-Brose, Justine ;

Couble, Pierre-Jean ;

Deehan, Maureen R. ;

Nelson, Robert J. ;

Ferlin, Walter G. ;

Lory, Sabrina .

JOURNAL OF IMMUNOLOGY RESEARCH, 2016, 2016

[15] The ESPOIR cohort: A ten-year follow-up of early arthritis in France: Methodology and baseline characteristics of the 813 included patients [J].

Combe, Bemard ;

Benessiano, Joealle ;

Berenbaum, Francis ;

Cantagrel, Alain ;

Daures, Jean-Pierre ;

Dougados, Maxime ;

Fardellone, Patrice ;

Fautrel, Bruno ;

Flipo, Rene-Marc ;

Goupille, Philippe ;

Guillemin, Francis ;

Le Loet, Xavier ;

Logeart, Isabelle ;

Marlette, Xavier ;

Meyer, Olvier ;

Ravaud, Philippe ;

Rincheval, Nathalle ;

Saraux, Alain ;

Schaeverbeke, Thierry ;

Sibilia, Jean .

JOINT BONE SPINE, 2007, 74 (05) :440-445

[16] Immunogenicity of protein therapeutics [J].

De Groot, Anne S. ;

Scott, David W. .

TRENDS IN IMMUNOLOGY, 2007, 28 (11) :482-490

[17]

Fay MP, 2010, J STAT SOFTW, V36, P1

[18]

Goekoop-Ruiterman YPM, 2005, ARTHRITIS RHEUM-US, V52, P3381, DOI [10.1002/art.21405, 10.1002/art.23364]

[19] Smokers run increased risk of developing anti-natalizumab antibodies [J].

Hedstrom, A. K. ;

Alfredssoni, L. ;

Ryner, M. Lundkvist ;

Fogdell-Hahn, A. ;

Hillert, Jan ;

Olsson, T. .

MULTIPLE SCLEROSIS JOURNAL, 2014, 20 (08) :1081-1085

[20] Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a [J].

Hedstrom, Anna Karin ;

Ryner, Malin ;

Fink, Katarina ;

Fogdell-Hahn, Anna ;

Alfredsson, Lars ;

Olsson, Tomas ;

Hillert, Jan .

MULTIPLE SCLEROSIS JOURNAL, 2014, 20 (04) :445-450

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