Intest Res.  2019 Jan;17(1):94-106. 10.5217/ir.2018.00048.

Long-term prognosis of Japanese patients with biologic-naïve Crohn’s disease treated with anti-tumor necrosis factor-α antibodies

• Moroi R
• Endo K
• Yamamoto K
• Naito T
• Onodera M
• Kuroha M
• Kanazawa Y
• Kimura T
• Kakuta Y
• Masamune A
• Kinouchi Y
• Shimosegawa T

• KMID: 2438448
• DOI: http://doi.org/10.5217/ir.2018.00048

Abstract

BACKGROUND/AIMS
Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn's disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments.
METHODS
This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model.
RESULTS
The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels < 2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics.
CONCLUSIONS
Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.

Keyword

Crohn disease; Infliximab; Adalimumab; Long-term prognosis

MeSH Terms

Adalimumab
Antibodies*
Asian Continental Ancestry Group*
Biological Products
C-Reactive Protein
Cohort Studies
Crohn Disease
Food, Formulated
Humans
Infliximab
Necrosis*
Prognosis*
Proportional Hazards Models
Retrospective Studies
Risk Factors
Serum Albumin
Adalimumab
Antibodies
Biological Products
C-Reactive Protein
Infliximab
Serum Albumin

Figure

• 

  Fig. 1. Diagram of the patients administered biologics. Two hundred and eighty-six patients were enrolled and 62 patients were excluded due to several reasons such as primary non-response and postoperative maintenance. IFX, infliximab; ADA, adalimumab.

• 

  Fig. 2. Overall long-term prognosis after starting biologics administration. (A) The combined cumulative retention rates (%) of the biologics per years of maintenance therapy. The cumulative retention rates of the biologics were 90%, 79%, and 73% at 1, 3, and 5 years, respectively. (B) The combined relapse-free survival rates (%) of the biologics per years of maintenance therapy. The cumulative relapse-free survivals were 80%, 54%, and 39% at 1, 3, and 5 years, respectively. (C) The combined surgery-free survival rates (%) of the biologics per years of maintenance therapy. The surgery-free survivals were 93%, 88%, and 83% at 1, 3, and 5 years, respectively. Number at risk below each graph refers to the number of patients at each time point (0, 1, 3, 5, and 10 years). Both the infliximab and adalimumab patient populations were analyzed together. Censoring is indicated by the tick.

• 

  Fig. 3. The comparisons of long-term outcomes between infliximab (IFX) and adalimumab (ADA) treatments. (A) The cumulative retentions rates (%) of each biologic per years of maintenance therapy. (B) The relapse-free survival rates (%) of each biologic per years of maintenance therapy. (C) The surgery-free survival rates (%) of each biologic per years of maintenance therapy. Below each graph is the number of patients at each time point (0, 1, 3, 5, and 10 years), for each treatment. There were no differences between IFX (n=144) and ADA (n=40) in the cumulative retention rates of biologics, the cumulative relapse-free survival and the surgery-free survival. Censoring is indicated by the tick.

• 

  Fig. 4. The differences of cumulative retention rates for each clinical factor. (A) The combined cumulative retention rates (%) of the biologics per years of maintenance therapy separated by sex. The cumulative retention rate was significantly higher in the male group (vs. female, P=0.0497). (B) The combined cumulative retention rates (%) of the biologics per years of maintenance therapy separated by concomitant elemental diet. The cumulative retention rate was significantly higher in the group with concomitant elemental diet of ≥900 kcal/day (vs. <900 kcal/day, P=0.0430). (C) The combined cumulative retention rates (%) of the biologics per years of maintenance therapy separated by baseline CRP levels. The cumulative retention rate was significantly higher in the group with the baseline CRP levels <2.6 mg/dL (vs. ≥2.6 mg/dL, P=0.0098). (D) The combined cumulative retention rates (%) of the biologics per years of maintenance therapy separated by baseline serum albumin levels. The cumulative retention rate was significantly higher in the group with the baseline serum albumin levels ≥3.5 g/dL (vs. <3.5 g/dL, P=0.0274). Number at risk below each graph refers to the number of patients at each time point (0, 1, 3, 5, and 10 years), separated by factor. Both the infliximab and adalimumab patient populations were analyzed together. Censoring is indicated by the tick.

• 

  Fig. 5. The differences in cumulative relapse-free and surgery-free survival rates depending on baseline albumin levels. (A) The combined relapse-free survival rates (%) and (B) the combined surgery-free survival rates (%) of the biologics per years of maintenance therapy depending on baseline albumin levels. The group with baseline serum albumin levels ≥3.5 g/dL showed significantly higher relapse-free and surgery-free survival rates than the group with baseline serum albumin levels <3.5 g/dL (P=0.0257 and P=0.0292, respectively). Number at risk below each graph refers to the number of patients at each time point (0, 1, 3, 5, and 10 years), for each albumin level group. Both the infliximab and adalimumab patient populations were analyzed together. Censoring is indicated by the tick.

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