Earlier Anti-Tumor Necrosis Factor Therapy of Crohn's Disease Correlates with Slower Progression of Bowel Damage

Abstract

Introduction: Crohn's disease (CD) follows a relapsing and remitting course incurring cumulative bowel damage over time. The question of whether or not the timing of the initiating biologic therapy affects long-term disease progression remains unanswered. Herein, we calculated rates of change in the Lémann index-which quantifies accumulated bowel damage-as a function of the time between the disease onset and initiation of biologic therapy. We aimed to explore the impact of the earlier introduction of biologics on the rate of progression of long-term cumulative bowel damage.

Methods: Medical records of CD patients treated during 2009-2014 at The Mount Sinai Hospital were queried. Inclusion criteria were two comprehensive assessments allowing calculation of the index at t₁ and t₂: two time-points ≥ 1 year apart. Patients with biologics introduced before or within 3 months at inclusion (t₁) were defined as Bio-pre-t₁ and those who did not as Bio-post-t₁. The rate of disease progression was calculated as the change in the index per year during t₁-t₂.

Results: A total of 88 patients were studied: 58 Bio-pre-t₁ and 30 Bio-post-t₁. Among the 58 Bio-pre-t₁ cases, damage progressed in 29 (50%), regressed in 20 (34.5%), and stabilized in 9 (15.5%). Median time to initiation of biologics among patients whose index improved was nominally shorter compared to that in patients whose index progressed (8 vs. 15 years). Earlier introduction of biologics tended to correlate with the slower rate of progression (ρ = 0.241; p = 0.069).

Conclusions: Earlier introduction of biologics tended to correlate with the slower progression of bowel damage in CD, reflected by the reduced rate of Lémann index progression.

Keywords: Adalimumab; Biological therapy; Crohn disease; Inflammatory bowel disease; Infliximab.

Fig. 1

CONSORT diagram depicting patient selection for the study. MRE MRI enterography; t₁ time point 1 when Li was assessed at inclusion; Bio-pre-t₁: biologics before or within 3 months of inclusion, i.e., t₁ Bio-post-t₁ no biologics or initiating biologics after 3 months of inclusion, i.e., t₁

Fig. 2

The Lémann index by disease duration at t₁; N = 88; coefficient, Kruskal–Wallis statistic = 13.79, p = 0.008)

Fig. 3

The Lémann index by disease duration at t₂; n = 88; Kruskal–Wallis test statistic = 15.99; p = 0.003

Fig. 4

Box-plots depicting distribution of the timing of initiating biologics among patients who received the treatment before or within 3 months of t₁ (n = 58) stratified by outcome of interest: damage arrest/regression; Wilcoxon–Mann–Whitney U test, p = 0.058

Fig. 5

Correlation between the rate of progression of the Lémann index of cumulative bowel damage on the Y-axis and the timing of initiating anti-TNF Therapy on X-axis among patients who received biologics prior of within 3 months of t₁: Bio-pre-t₁, n = 58; correlation coefficient Spearman’s ρ = 0.241; p = 0.069

Fig. 6

Correlation between the rate of progression of the Lémann index of cumulative bowel damage on the Y-axis and the timing of initiating anti-TNF Therapy on X-axis among patients who received biologics either after 3 months of t₁ or did not receive any biologics during the study period: Bio-post-t₁, n = 30; correlation coefficient Spearman’s ρ = −0.024; p = 0.934