Background
Approximately 20-30% of individuals with Crohn's disease (CD) experience a relatively mild disease course without progression. However, there is no widely accepted objective definition of mild CD. We aimed to identify endoscopic severity cut-offs that can be used to define mild non-progressive CD.

Methods
We performed a multicenter retrospective study utilizing cohorts from two tertiary care centers – Massachusetts General Hospital (PRISM) and Mount Sinai Hospital (MSCCR). Included patients were defined as mild based on their natural history with no prior CD surgical history and no use of immunomodulator or biologic therapy at the time of endoscopic assessment. Endoscopic severity was scored prospectively using the simple endoscopic score for CD (SES-CD). The primary outcome was disease progression defined as need for systemic steroids, biologic or immunomodulator therapy initiation, development of new stricturing or penetrating complications, or CD-related hospitalization or surgery. Univariable and multivariable Cox proportional hazards modeling identified predictors of the primary outcome at 2 and 5 years following endoscopic assessment.

Results
The final study cohort comprised 146 patients. Cohort characteristics are summarized in Table 1. The composite primary outcome of disease progression occurred in 27% and 39% of patients at years 2 and 5, respectively (Figure 1A). Endoscopic severity at enrollment independently predicted disease progression at both 2 and 5 years. Fewer than one-fifth (19%) of patients with SES-CD of 0 had disease progression at 2 years compared to 45% of those with SES-CD ≥ 7 (P = 0.002). Compared to those with an SES-CD score of 0, an SES-CD ≥ 7 had a greater risk of progression at 2 years (HR 2.48, 95% CI 1.10 – 5.62) and 5 years (HR 2.86, 95% CI 1.41 – 5.81). Compared to SES-CD score of 0, there was no significantly increased risk of disease progression with an SES-CD of 1-3 (HR 1.21, 95% CI 0.50 – 2.90 at 2 years, HR 1.46. 95% CI 0.66 – 2.83 at 5 years) or 4-6 (HR 1.94, 95% CI 0.70 – 5.39 at 2 years, HR 1.92, 95% CI 0.80 – 4.60 at 5 years) (Figure 1B). Other variables associated with disease progression were female gender (HR 1.94, 95% CI 1.14 – 3.31), prior immunomodulator use (HR 3.27, 95% CI 1.92 – 5.59), prior biologic use (2.52, 95% CI 1.36 – 4.64), and shorter disease duration (HR 0.95 per 1 year, 95% CI 0.93- 0.98). SES-CD score > 7 remained independently predictive of disease progression among the 99 immunomodulator- and biologic-naïve patients (p=0.049).

Conclusions
In patients with established long-standing mild CD, SES-CD ≥ 7 independently predicts disease progression suggesting a score ≤ 6 may be used to identify patients who are least likely to progress over the subsequent five years and may be considered as part of the definition of mild CD.

Henrik Albaek Jacobsen

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