期刊
JOURNAL OF CROHNS & COLITIS
卷 9, 期 3, 页码 238-245出版社
OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjv004
关键词
IBD; infliximab; loss of response; dose optimization; dose intensification; antibodies against IFX; therapeutic drug monitoring
资金
- Aase and Ejnar Danielsen's Foundation
- Beckett Foundation
- Danish Biotechnology Program
- Danish Colitis-Crohn Society
- Danish Medical Association Research Foundation
- Frode V. Nyegaard and Wife's Foundation
- Health Science Research Foundation of Region of Copenhagen
- Herlev Hospital Research Council
- Lundbeck Foundation
- P. Carl Petersen's Foundation
- Ole Ostergaard Thomsen's Research Foundation
- Jorn Brynskov's Research Foundation
Background and aims: Intensification of the infliximab (IFX) regimen is recommended if the treatment effect is inadequate. However, the rationale for this is not well defined as the underlying mechanisms vary. The aim of this study was to explore the association between changes in serum IFX and anti-IFX antibodies (Abs) after IFX intensification and clinical outcomes. Methods: We performed a post hoc analysis of a randomized clinical trial including 42 Crohn's disease patients with IFX treatment failure, all treated with an intensified IFX regimen (5 mg/kg every 4 week) for 12 weeks. Trough serum IFX and anti-IFX Ab concentrations were measured by a homogeneous mobility shift binding assay (HMSA) and a functional cell-based reporter gene assay (RGA) at treatment failure and the end of the trial. Results: Twenty-one patients (50%) regained clinical response on the intensified IFX regimen. The increase in serum trough levels of IFX during treatment intensification was higher among responders than non-responders (RGA, 8.8 versus 3.0 mu g/mL, p = 0.035; HMSA, 9.9 versus 4.7 mu g/mL, p = 0.040), and differentiated patients by clinical outcome (RGA, area under receiver operating characteristic curve [AUC] 0.75 [0.53-0.97], p = 0.035; HMSA, AUC 0.74 [0.53-0.95], p = 0.042). All responders exhibited an IFX increase >= 2.6 mu g/mL (sensitivity 100%, specificity 50%). Anti-IFX Abs detected by HMSA in 13 patients (32%) were often non-functional and became undetectable during IFX intensification. However, even functional anti-IFX Abs detected by RGA in six patients (15%) became undetectable. Conclusion: Increase in IFX levels following treatment intensification was associated with improved clinical outcomes, indicating insufficient drug levels in a subgroup of patients. Anti-IFX Abs may become undetectable during treatment intensification, suggesting lowered production or the formation of immune complexes.
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