当前位置： SCI文献检索 > INFLAMMATORY BOWEL DISEASES期刊下所有文献 > Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.

Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.

Abstract：

BACKGROUND:A notable proportion of patients with inflammatory bowel disease (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if immunogenicity of IFX influenced immunogenicity and clinical outcomes of later ADL therapy. METHODS:Single-center cohort study including all patients with IBD assessed for antibodies (Abs) against IFX or ADL. RESULTS:Anti-IFX Abs were evaluated in 187 patients treated with IFX as first line anti-TNF agent. Approximately, half (49%) were positive. Detected anti-IFX Abs had functional capacity as judged by a median IFX concentration below limit of detection (interquartile range, 0.0-0.0 μg/mL) versus 3.8 μg/mL (IQR, 1.3-7.9) in anti-IFX Ab-negative patients, P < 0.0001; but did not cross-react with ADL. Anti-ADL Abs were assessed in 57 ADL-treated patients. Twelve (21%) tested positive. Patients with previous anti-IFX Ab development were significantly more prone to develop anti-ADL Abs (33%) than those without (0%): odds ratio estimated 11, P = 0.04. The anti-ADL Abs were also functional because ADL was undetectable in all anti-ADL Ab-positive patients versus median 8.3 μg/mL (IQR 5.0-11.0) in anti-ADL-negative patients, P < 0.0001. The presence of anti-ADL Abs increased the risk of secondary ADL treatment failure with OR 28 (3-248), P < 0.001. ADL trough levels, irrespectively of anti-ADL Ab status, associated with efficacy of ADL maintenance therapy: AUC(ROC) 0.77 (0.62-0.93), P < 0.01. CONCLUSIONS:Switchers with anti-IFX Abs are prone to develop de novo anti-ADL Abs, which may result in therapeutic failure. Assessment of ADL immunogenicity in anti-IFX Ab-positive switchers is required to ensure optimal interventions at inadequate treatment responses and to avoid inappropriate ADL intensification regimens.

journal_name

Inflamm Bowel Dis

journal_title

Inflammatory bowel diseases

authors

Frederiksen MT,Ainsworth MA,Brynskov J,Thomsen OO,Bendtzen K,Steenholdt C

doi

10.1097/MIB.0000000000000138

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

1714-21

issue

eissn

1078-0998

issn

1536-4844

journal_volume

pub_type

临床试验,杂志文章

在线工具

Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.