Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease.
Aliment Pharmacol Ther
; 37(12): 1172-83, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23650912
ABSTRACT
BACKGROUND:
Infliximab (IFX) is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, human anti-murine immunoglobulin Abs are common and may cross-react with the murine part of IFX.AIM:
To investigate if Abs binding to IFX's Fab region (IFX-Fab) are present in IBD patients before exposure to IFX, and whether they predict efficacy and safety of IFX therapy.METHODS:
Observational, retrospective cohort study of patients with CD (n = 29) and UC (n = 22).RESULTS:
Pre-treatment levels of IFX-Fab reactive IgG Abs were significantly lower in CD patients in remission after 1 year of maintenance IFX (median 91 mU/L, n = 8) than in the rest of the patients (639 mU/L, n = 21; P < 0.01), and lower than in patients with secondary loss of response in particular (692 mU/L, n = 7; P < 0.01). A cut-off concentration of <439 mU IFX-Fab reactive IgG Ab per litre comprised all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. The pre-treatment levels of IFX-Fab reactive IgG Abs were markedly higher in patients developing infusion reactions to IFX (1037 mU/L, n = 7) than in the remaining patients (349 mU/L, n = 44; P = 0.036).CONCLUSIONS:
IFX-Fab reactive IgG antibodies present in serum from IBD patients before infliximab therapy associate with lack of long-term efficacy and safety. Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanised agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Gastrointestinais
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Imunoglobulina G
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Fragmentos Fab das Imunoglobulinas
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Doenças Inflamatórias Intestinais
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Anticorpos Monoclonais
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Ano de publicação:
2013
Tipo de documento:
Article