Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000

Abstract

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Figure 1

The workflow of the study. The analysis of change in age at onset and association analysis in treatment selection was performed.

Figure 2

Changes in age at onset. The age at onset of both ulcerative colitis (UC) (a) and Crohn’s disease (CD) (b) has increased over time.

Figure 3

Proportion of patients with inflammatory bowel diseases (IBD) who have been prescribed each mediation in expert hospitals versus nonexpert community hospitals. (a) The proportion of patients with UC who have been prescribed each mediation in expert hospitals versus nonexpert community hospitals. The treatment strategies shown in the figure are based on the Japanese treatment guidelines for UC. (b) The proportion of patients with CD who have been prescribed each mediation in expert hospitals versus nonexpert community hospitals. The treatment strategies shown in the figure are based on the Japanese treatment guidelines for CD.

Figure 4

Association analysis in the patients with IBD who were diagnosed in the prebiologic and biologic eras. (a) The grouped matrix-based visualization combination in patients with UC diagnosed in the prebiologic era. In a balloon plot with antecedent medication groups as columns and consequent drugs as rows, the color represents the aggregated lift in the group and the size shows the aggregated support. The numbers of antecedent medication combinations with the names of the most frequently appeared drugs are displayed as the labels in the columns. The combinations between antecedent groups and a consequent drug with the highest lift value were placed in the upper left of this matrix, and the combinations were placed in the lower right according to the decrease in the lift value. (b) The rank of the top 10 treatment combination in patients with UC diagnosed in the prebiologic era (see description of the plot in Suppl. Figure 5). Each disc indicates the combination between an antecedent medication and a consequent drug with a top 10 high lift value. The support value was 0.0041 and the lift value was 49.0. (c) The grouped matrix-based visualization combination in patients with UC diagnosed in the biologic era. (d) The rank of the top 10 treatment combination in patients with UC diagnosed in the biologic era. The support value was 0.0036 and the lift value was 56.0. (e) The grouped matrix-based visualization combination in patients with CD diagnosed in the prebiologic era. (f) The rank of the top 10 treatment combination in patients with CD diagnosed in the prebiologic era. The disc size indicates the support value (0.0227–0.0455) and the lift value was 10.1. (g) The grouped matrix-based visualization combination in patients with CD diagnosed in the biologic era. (h) The rank of the top 10 treatment combination in patients with CD diagnosed in the biologic era. The support value was 0.0071 and the lift value was 10.1.