Intest Res.  2022 Oct;20(4):464-474. 10.5217/ir.2021.00139.

Long-term clinical and real-world experience with Crohn’s disease treated with anti-tumor necrosis factor-α antibodies

• Otake H
• Matsumoto S
• Mashima H

• KMID: 2535820
• DOI: http://doi.org/10.5217/ir.2021.00139

Abstract

Background/Aims
Although anti-tumor necrosis factor (TNF)-α agents are important therapeutic drugs for Crohn’s disease (CD), data regarding their long-term sustained effects are limited. Herein, we evaluated the long-term loss of response (LOR) to anti-TNF-α agents in patients with CD.
Methods
This retrospective study included patients with CD who started treatment with infliximab or adalimumab as a first-line therapeutic approach. The cumulative event-free, retention, and surgery-free rates after the start of biological therapy were analyzed. Secondary LOR was analyzed in patients who achieved corticosteroid-free clinical remission after the start of biological therapy. Cox proportional hazards models were used to analyze the predictive factors of secondary LOR.
Results
The cumulative event-free rates at 1, 2, 5, and 10 years were 83.3%, 75.1%, 37.4%, and 23.3%, respectively. The incidence of LOR was 10.6% per patient-year of follow-up. At 12–14 weeks after the start of biological therapy, the proportion of patients with a C-reactive protein to albumin (CRP/ALB) ratio ≥0.18 was significantly higher in patients with LOR (P<0.001). Multivariate analysis indicates that a CRP/ALB ratio ≥0.18 (hazard ratio [HR], 5.86; 95% confidence interval [CI], 1.56–22.0; P=0.009) and upper gastrointestinal tract inflammation (HR, 3.00; 95% CI, 1.26–7.13; P=0.013) were predictive factors of secondary LOR.
Conclusions
Although anti-TNF-α agents contributed to long-term clinical remission of CD, the annual incidence of secondary LOR was 10.6%. The CRP/ALB ratio at 3 months after the start of biological therapy and upper gastrointestinal tract inflammation were identified as predictive factors of secondary LOR.

Keyword

Crohn disease; Infliximab; Adalimumab; Loss of response; C-reactive protein to albumin ratio

Figure

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  Fig. 1. (A) Kaplan-Meier analysis of the cumulative event-free rate. (B) Kaplan-Meier analysis of the cumulative retention rate. (C) Kaplan-Meier analysis of the cumulative dose escalation-free rate. (D) Kaplan-Meier analysis of the cumulative surgery-free rate. (E) Kaplan-Meier analysis of the cumulative event-free rate in the infliximab (IFX) group and the adalimumab (ADA) group. (F) Kaplan-Meier analysis of the cumulative retention rate in the IFX group and the ADA group. (G) Kaplan-Meier analysis of the cumulative dose escalation-free rate in the IFX group and the ADA group. (H) Kaplan-Meier analysis of the cumulative surgery-free rate in the IFX group and the ADA group.

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  Fig. 2. Receiver operating characteristics curve for predicting secondary loss of response (cutoff, 0.184; sensitivity, 0.553; specificity, 0.871; AUC, 0.713). AUC, area under the curve; CRP/ALB ratio, ratio of C-reactive protein to albumin.

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  Fig. 3. (A) Kaplan-Meier analysis of the cumulative relapse-free rate. (B) Kaplan-Meier analysis of the cumulative relapse-free rate in the CRP/ALB ratio ≥0.18 group and CRP/ALB ratio <0.18 group. (C) Kaplan-Meier analysis of the cumulative relapse-free rate in infliximab (IFX) group and the adalimumab (ADA) group. (D) Kaplan-Meier analysis of the cumulative relapse-free rate by concomitant immunomodulator status. CRP/ALB ratio, ratio of C-reactive protein to albumin.

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  Fig. 4. (A) Kaplan-Meier analysis of the cumulative event-free rate after dose escalation. (B) Kaplan-Meier analysis of the cumulative event-free rate after dose escalation in the infliximab (IFX) group and the adalimumab (ADA) group.

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