A risk score system to timely manage treatment in Crohn's disease: a cohort study

Abstract

Background: Clinical severity and intestinal lesions of Crohn's disease (CD) usually progress over time and require a step up adjustment of the therapy either to prevent or to treat complications. The aim of the study was to develop a simple risk scoring system to assess in individual CD patients the risk of disease progression and the need for more intensive treatment and monitoring.

Methods: Prospective cohort study (January 2002-September 2014) including 160 CD patients (93 female, median age 31 years; disease behavior (B)1 25%, B2 55.6%, B3 19.4%; location (L)1 61%, L3 31.9%, L2 6%; L4 0.6%; perianal disease 28.8%) seen at 6-12-month interval. Median follow-up 7.9 years (IQR: 4.3-10.5 years). Poisson models were used to evaluate predictors, at each clinical assessment, of having the following outcomes at the subsequent clinical assessment a) use of steroids; b) start of azathioprine; c) start of anti-TNF-α drugs; d) need of surgery. For each outcome 32 variables, including demographic and clinical characteristics of patients and assessment of CD intestinal lesions and complications, were evaluated as potential predictors. The predictors included in the model were chosen by a backward selection. Risk scores were calculated taking for each predictor the integer part of the Poisson model parameter.

Results: Considering 1464 clinical assessments 12 independent risk factors were identified, CD lesions, age at diagnosis < 40 years, stricturing behavior (B2), specific intestinal symptoms, female gender, BMI < 21, CDAI> 50, presence of inflammatory markers, no previous surgery or presence of termino-terminal anastomosis, current use of corticosteroid, no corticosteroid at first flare-up. Six of these predicted steroids use (score 0-9), three to start azathioprine (score 0-4); three to start anti-TNF-α drugs (score 0-4); six need of surgery (score 0-11). The predicted percentage risk to be treated with surgery within one year since the referral assessment varied from 1 to 28%; with azathioprine from 3 to 13%; with anti-TNF-α drugs from 2 to 15%.

Conclusions: These scores may provide a useful clinical tool for clinicians in the prognostic assessment and treatment adjustment of Crohn's disease in any individual patient.

Keywords: Crohn’s disease; Risk factors, small intestine contrast ultrasonography; Risk score system; Therapy, medical, surgical.

Fig. 1

a Box-and-whiskers plots of BMI across 13 years follow-up period. The boxes at each score extend from the 25th percentile (× [25]) to the 75th percentile (×[75]) [i.e., the interquartile range (IQ)]; the lines inside the boxes represent the median values. The line emerging from the boxes (i.e., the “whiskers”) extend to the upper and lower adjacent values. The upper adjacent value is defined as the largest data point × [75] + 1.5 × IQ, and the lower adjacent value is defined as the smallest data point × [25] – 1.5 × IQ. Observed values more extreme than the adjacent values, if any, are individually plotted (circles). BMI (Kg/m²): body mass index. b Box-and-whiskers plots of CDAI across 13 years follow-up period. The boxes at each score extend from the 25th percentile (× [25]) to the 75th percentile (× [75]) [i.e., the interquartile range (IQ)]; the lines inside the boxes represent the median values. The line emerging from the boxes (i.e., the “whiskers”) extend to the upper and lower adjacent values. The upper adjacent value is defined as the largest data point × [75] + 1.5 × IQ, and the lower adjacent value is defined as the smallest data point × [25] – 1.5 × IQ. Observed values more extreme than the adjacent values, if any, are individually plotted (circles). CDAI: Crohn’s disease activity index

Fig. 2

a Estimated cumulative probability of using corticosteroids by month after referral visit for patients with different total score. A patient scoring 1 (e.g., CD complications at SICUS, age at diagnosis ≥40 years, B1 behavior, absence of specific symptoms, presence of colon-ileal reflux at SICUS) has 1.6% and 3.1% probability of using corticosteroids at 6 months and at 1 year since the referral visit, respectively; a patient scoring 9 (e.g., CD intestinal lesions > 20 cm and no complications at SICUS, age at diagnosis < 40 years, B2 behavior, presence of specific symptoms, absence of colon-ileal reflux at SICUS) has 17.6% and 32.2% probability of using corticosteroids at 6 months and at 1 year since the referral visit, respectively. Dotted line: score 1; continuous line: score 9. b Observed vs model-predicted at one year since the referral visit of using corticosteroids by groups of score

Fig. 3

a Estimated cumulative probability of start azathioprine by month after referral visit for patients with different total score. b Observed vs model-predicted at one year since the referral visit of start azathioprine by groups of score

Fig. 4

a Estimated cumulative probability of start anti-TNF α drugs by month after referral visit for patients with different total score. b Observed vs model-predicted at one year since the referral visit of start anti-TNF- α drugs by groups of score

Fig. 5

a Estimated cumulative probability of need of surgery by month after referral visit for patients with different total score. b Observed vs model-predicted at one year since the referral visit of need of surgery by groups of score