Anti-infliximab antibodies in inflammatory bowel disease: prevalence, infusion reactions, immunosuppression and response, a meta-analysis

被引:63
作者
Lee, Lennard Y. W. [1 ]
Sanderson, Jeremy D. [1 ]
Irving, Peter M. [1 ]
机构
[1] Guys & St Thomas NHS Fdn Trust, Dept Gastroenterol, London SE1 7EH, England
关键词
anti-infliximab antibodies; human antichimeric antibodies; inflammatory bowel disease; infusion reactions; CROHNS-DISEASE; MAINTENANCE THERAPY; HYDROCORTISONE PREMEDICATION; SERUM INFLIXIMAB; IMMUNOGENICITY; EFFICACY; AZATHIOPRINE; ELIMINATION; REMISSION; TRIAL;
D O I
10.1097/MEG.0b013e32835558cf
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha. When used in inflammatory bowel disease, primary nonresponse is found in at least 10% of patients, with secondary loss of response occurring in a further 10-15% per year. It has been suggested that this may in part be a result of the development of anti-infliximab antibodies (ATIs). The aim of the study was to determine in patients receiving infliximab the prevalence of ATIs, the effect of immunosuppressants on the prevalence of ATI, the effect of ATIs on the prevalence of infusion reactions and the effect of ATIs on the rates of remission. MEDLINE and EMBASE databases were searched from 1948 and 1980, respectively, to October 2011. Eighteen studies involving 3326 patients were included. The prevalence of ATIs was 45.8% when episodic infusions of infliximab were given and 12.4% when maintenance infliximab was given. The rates of infusion reactions were significantly higher in patients with ATIs (relative risk: 2.07; 95% confidence interval, 1.61-2.67). Immunosuppressants resulted in a 50% reduction in the risk of developing ATIs (P<0.00001). However, the presence or absence of ATIs did not affect the rates of clinical remission. The prevalence of ATIs depends on the regimen of infliximab administration and the use of immunosuppressants. Patients who test positive for ATIs are at an increased risk of infusion reactions, but have similar rates of remission compared with patients who test negative for ATIs. Further analysis is required to determine whether loss of response is dependent on the titre of ATIs. Eur J Gastroenterol Hepatol 24: 1078-1085 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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页码:1078 / 1085
页数:8
相关论文
共 32 条
[1]   Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Concentrations in Patients With Inflammatory Bowel Disease [J].
Afif, Waqqas ;
Loftus, Edward V., Jr. ;
Faubion, William A. ;
Kane, Sunanda V. ;
Bruining, David H. ;
Hanson, Karen A. ;
Sandborn, William J. .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2010, 105 (05) :1133-1139
[2]   Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease [J].
Ainsworth, Mark A. ;
Bendtzen, Klaus ;
Brynskov, Jorn .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2008, 103 (04) :944-948
[3]   Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease [J].
Baert, F ;
Noman, M ;
Vermeire, S ;
Van Assche, G ;
D'Haens, G ;
Carbonez, A ;
Rutgeerts, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (07) :601-608
[4]   The immunogenic part of infliximab is the F(ab′)2, but measuring antibodies to the intact infliximab molecule is more clinically useful [J].
Ben-Horin, Shomron ;
Yavzori, Miri ;
Katz, Lior ;
Kopylov, Uri ;
Picard, Orit ;
Fudim, Ella ;
Coscas, Daniel ;
Bar-Meir, Simon ;
Goldstein, Itamar ;
Chowers, Yehuda .
GUT, 2011, 60 (01) :41-48
[5]   Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies [J].
Bendtzen, Klaus ;
Ainsworth, Mark ;
Steenholdt, Casper ;
Thomsen, Ole Ostergaard ;
Brynskov, Jorn .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2009, 44 (07) :774-781
[6]   Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease [J].
Candon, S ;
Mosca, A ;
Ruemmele, F ;
Goulet, O ;
Chatenoud, L ;
Cézard, JP .
CLINICAL IMMUNOLOGY, 2006, 118 (01) :11-19
[7]   Incidence and Clinical Significance of Immunogenicity to Infliximab in Crohn's Disease: A Critical Systematic Review [J].
Cassinotti, Andrea ;
Travis, Simon .
INFLAMMATORY BOWEL DISEASES, 2009, 15 (08) :1264-1275
[8]   Early serial trough and antidrug antibody level measurements predict clinical outcome of infliximab and adalimumab treatment [J].
Casteele, N. Vande ;
Ballet, V. ;
Van Assche, G. ;
Rutgeerts, P. ;
Vermeire, S. ;
Gils, A. .
GUT, 2012, 61 (02) :321-321
[9]   Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease. [J].
Colombel, Jean Frederic ;
Sandborn, William J. ;
Reinisch, Walter ;
Mantzaris, Gerassimos J. ;
Kornbluth, Asher ;
Rachmilewitz, Daniel ;
Lichtiger, Simon ;
D'Haens, Geert ;
Diamond, Robert H. ;
Broussard, Delma L. ;
Tang, Kezhen L. ;
van der Woude, C. Janneke ;
Rutgeerts, Paul .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (15) :1383-1395
[10]  
Drastich P, 2011, GASTROENTEROLOGY, V140, pS292