Prevalence of Anti-infliximab Antibodies and Their Associated Co-factors in Children with Refractory Arthritis and / or Uveitis: A Retrospective Longitudinal Cohort Study

被引:11
作者
Aeschlimann, Florence A.
Angst, Felix
Hofer, Kevin D.
Schneider, Elvira Cannizzaro
Schroeder-Kohler, Silke
Lauener, Roger
van der Kleij, Desiree
Rispens, Theo
Saurenmann, Rotraud K.
机构
[1] Univ Childrens Hosp, Dept Rheumatol, Zurich, Switzerland
[2] RehaClin Bad Zurzach, Bad Zurzach, Switzerland
[3] Ostschweizer Sauglings & Kinderspital, Dept Pediat, St Gallen, Switzerland
[4] Sanquin, Lab Biologicals, Amsterdam, Netherlands
[5] Sanquin Res, Dept Immunopathol, Amsterdam, Netherlands
[6] Landsteiner Acad Med Ctr, Amsterdam, Netherlands
[7] Kantonsspital Winterthur, Dept Pediat, Winterthur, Switzerland
关键词
INFLIXIMAB; ANTICHIMERIC ANTIBODIES; UVEITIS; JUVENILE IDIOPATHIC ARTHRITIS; INFUSION REACTIONS; JUVENILE IDIOPATHIC ARTHRITIS; OF-RHEUMATOLOGY RECOMMENDATIONS; ALPHA MONOCLONAL-ANTIBODY; CROHNS-DISEASE; INTRAVENOUS INFUSIONS; INHIBITOR DEVELOPMENT; PLUS METHOTREXATE; ADVERSE EVENTS; THERAPY; IMMUNOGENICITY;
D O I
10.3899/jrheum.160072
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. Infliximab (IFX) is a monoclonal tumor necrosis factor-a-inhibiting antibody used in children with refractory arthritis and uveitis. Immunogenicity is associated with a lack of clinical response and infusion reactions in adults; data on immunogenicity in children treated with IFX for rheumatic diseases are scarce. We aimed to describe the prevalence of anti-IFX antibodies and determine co-factors associated with anti-IFX antibodies in children with inflammatory rheumatic and ocular diseases. Methods. Consecutive children treated between August 2009 and August 2012 with IFX at our department were included. Blood samples were collected every 6 months before IFX infusion and tested for anti-IFX antibodies by radioimmunoassay. Patients ' charts were retrospectively reviewed for clinical features and analyzed for associations with anti-IFX antibodies. Results. Anti-IFX antibodies occurred in 14/62 children (23%) and 32/253 blood samples (12.6%) after a mean treatment time of 1084 days (range 73-3498). Infusion reactions occurred in 10/62 (16%) children during the treatment period. With continuation of IFX, anti-IFX antibodies disappeared in 7/14 children. In the bivariate analysis, the occurrence of anti-IFX antibodies was associated with younger age at IFX treatment start (mean age 7.01 vs 9.88 yrs, p = 0.003) and infusion reactions (OR 15.0), while uveitis as treatment indication was protective against development of anti-IFX antibodies (OR 0.17), likely because of higher IFX doses. In the multivariate logistic regression, all 3 covariates remained highly significant. Conclusion. Anti-IFX antibodies occurred commonly at any time during IFX treatment. Anti-IFX antibodies were associated with younger age at IFX start, infusion reactions, and arthritis as treatment indication.
引用
收藏
页码:334 / 341
页数:8
相关论文
共 45 条
[1]   Immunogenicity of anti-tumor necrosis factor antibodies - toward improved methods of anti-antibody measurement [J].
Aarden, Lucien ;
Ruuls, Sigrid R. ;
Wolbink, Gertjan .
CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (04) :431-435
[2]   Infliximab in Pediatric Rheumatology Patients: A Retrospective Analysis of Infusion Reactions and Severe Adverse Events During 2246 Infusions over 12 Years [J].
Aeschlimann, Florence A. ;
Hofer, Kevin D. ;
Schneider, Elvira Cannizzaro ;
Schroeder, Silke ;
Lauener, Roger ;
Saurenmann, Rotraud K. .
JOURNAL OF RHEUMATOLOGY, 2014, 41 (07) :1409-1415
[3]   Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion reaction to infliximab in patients with rheumatoid arthritis [J].
Augustsson, Jenny ;
Eksborg, Staffan ;
Ernestam, Sofia ;
Gullstrom, Eleanor ;
van Vollenhoven, Ronald .
ANNALS OF THE RHEUMATIC DISEASES, 2007, 66 (11) :1462-1466
[4]   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
[5]   2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features [J].
Beukelman, Timothy ;
Patkar, Nivedita M. ;
Saag, Kenneth G. ;
Tolleson-Rinehart, Sue ;
Cron, Randy Q. ;
DeWitt, Esi Morgan ;
Ilowite, Norman T. ;
Kimura, Yukiko ;
Laxer, Ronald M. ;
Lovell, Daniel J. ;
Martini, Alberto ;
Rabinovich, C. Egla ;
Ruperto, Nicolino .
ARTHRITIS CARE & RESEARCH, 2011, 63 (04) :465-482
[6]   Detection of infliximab levels and anti-infliximab antibodies: a comparison of three different assays [J].
Casteele, N. Vande ;
Buurman, D. J. ;
Sturkenboom, M. G. G. ;
Kleibeuker, J. H. ;
Vermeire, S. ;
Rispens, T. ;
van der Kleij, D. ;
Gils, A. ;
Dijkstra, G. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2012, 36 (08) :765-771
[7]   Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A [J].
Chalmers, E. A. ;
Brown, S. A. ;
Keeling, D. ;
Liesner, R. ;
Richards, M. ;
Stirling, D. ;
Thomas, A. ;
Vidler, V. ;
Williams, M. D. ;
Young, D. .
HAEMOPHILIA, 2007, 13 (02) :149-155
[8]   Immunomodulatory therapy with tumour necrosis factor α inhibitors in children with antinuclear antibody-associated chronic anterior uveitis: long-term results [J].
Doycheva, Deshka ;
Zierhut, Manfred ;
Blumenstock, Gunnar ;
Stuebiger, Nicole ;
Januschowski, Kai ;
Voykov, Bogomil ;
Deuter, Christoph .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2014, 98 (04) :523-528
[9]   Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: A randomized controlled trial [J].
Farrell, RJ ;
Alsahli, M ;
Jeen, YT ;
Falchuk, KR ;
Peppercorn, MA ;
Michetti, P .
GASTROENTEROLOGY, 2003, 124 (04) :917-924
[10]   Pharmacokinetic Properties of Infliximab in Children and Adults with Crohn's Disease: A Retrospective Analysis of Data from 2 Phase III Clinical Trials [J].
Fasanmade, Adedigbo A. ;
Adedokun, Omoniyi J. ;
Blank, Marion ;
Zhou, Honghui ;
Davis, Hugh M. .
CLINICAL THERAPEUTICS, 2011, 33 (07) :946-964