Factors associated with the loss of response to infliximab in patients with Crohn's disease
| Autor: | Akihiro Yamada, Yasushi Yoshimatsu, Nobuo Takada, Koji Sono, Yasuo Suzuki |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Immunology Antigen-Antibody Complex Activity index Biochemistry Gastroenterology Antibodies to infliximab Maintenance therapy Crohn Disease Internal medicine medicine Immunology and Allergy Humans In patient Molecular Biology Aged Demography Crohn's disease biology business.industry C-reactive protein Models Immunological Antibodies Monoclonal Hematology Middle Aged medicine.disease Infliximab C-Reactive Protein Treatment Outcome Antibodies Antinuclear biology.protein Blood Component Removal Female Antibody business medicine.drug |
| Zdroj: | Cytokine. 59(2) |
| ISSN: | 1096-0023 |
| Popis: | The efficacy of infliximab (IFX) has validated the role of TNF-α in the immunopathogenesis of Crohn's disease (CD). However, antibodies to IFX emerge, which impair its efficacy. This study investigated factor(s) associated with the loss of response (LOR) to IFX and how IFX non-responders may be treated.Seventy-four patients, 36 IFX responders (GI) and 38 with LOR (GII) were included. Trough IFX level, CD activity index (CDAI) and immunological markers during IFX maintenance therapy were measured. Adsorptive granulocyte/monocyte apheresis (GMA) was applied to patients with LOR.The durations of CD, 9.3 ± 5.5 yr and IFX therapy, 3.4 ± 2.0 yr in GII were longer vs GI (P=0.02, P=0.01). Similarly, C-reactive protein (P0.0001) and CDAI (P0.0001) in GII were higher. The median trough IFX was 4.7 μg/mL in GI and 8.4 μg/mL in GII, while the dose frequency was 8 weeks in GI and 4 weeks in GII. Soluble interleukin-2 receptor (sIL-2R) was higher in GII vs GI (P0.001). Seropositive rates of anti-nuclear antibodies (ANA) and circulating immune complexes (CIC) in GII were 50.0% and 68.4%, significantly higher vs GI (P0.05, P0.01). Patients with LOR duration1.5 yr showed higher CDAI and sIL-2R (P0.05) vs patients with LOR duration1.5 yr. Fifteen GII patients received GMA plus IFX combination and 46.7% responded. IL-10 increased in GMA-responders (P0.05), while CIC and ANA decreased (P=0.0237, P=0.0463).Patients with LOR to IFX had dysregulated immune response despite uncompromised trough IFX level. Further, inadequate T-cell differentiation by IFX was suggested. GMA appeared to benefit LOR patients by immunoregulation. |
| Databáze: | OpenAIRE |
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