Ultrasound remission after biologic induction and long-term endoscopic remission in Crohn's disease: a prospective cohort study.

Background: The Bowel Ultrasound Score (BUSS) accurately detects therapy-related changes by using the Simple Endoscopic Score for Crohn's disease (SES-CD) as the reference standard. We aimed to evaluate ultrasound remission as a treatment target and its prediction for long-term endoscopic remission. Methods: This single-centre prospective observational study, based at a tertiary referral centre in Milan, Italy, enrolled, between March 1, 2018, and January 31, 2021, adult patients with active CD (SES-CD >2) who were starting biologics. Colonoscopy and IUS was performed at baseline and at 12 months (mean 12.8 ± 4.2). The primary outcome was the predictive value of ultrasound remission at week 12 (BUSS ≤3.52) for long-term endoscopic remission at 12 months. The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was also calculated and optimal cut-point to detect endoscopic remission was identified through ROC analysis. Findings: 93 patients with CD were included. Of these, 22 patients (24%) achieved endoscopic remission. Week 12 ultrasound remission predicted endoscopic remission (59% compared with 41% of the patients who were not in ultrasound remission; OR 9.93, 95% CI 3.10-31.80; p < 0.001), while week 12 calprotectin values (<50, <100, <250 µg/g) did not. Week 12 ultrasound activity was associated with failure to achieve long-term endoscopic remission (NPV 87%, PPV 54%). IBUS-SAS cut-off to discriminate endoscopic remission was 22.8 (AUC 0.906). ROC curve comparison showed no-significant difference between BUSS and IBUS-SAS (p = 0.46) for detecting endoscopic remission. Interpretation: Early ultrasound remission predicts long-term endoscopic remission, making it a valuable early treatment target for clinical practice and in clinical trials. Larger multicentre validation studies are warranted to confirm these findings. Funding: None.

Early Intestinal Ultrasound Predicts Long-Term Endoscopic Response to Biologics in Ulcerative Colitis.

BACKGROUND AND AIMS: The Milan ultrasound criteria [MUC] is a validated score to assess endoscopic activity in ulcerative colitis [UC]. MUC > 6.2 detects Mayo endoscopic score [MES] > 1. In this study we evaluated the predictive value of MUC for biologic treatment response, using colonoscopy [CS] as a reference standard. METHODS: Consecutive UC patients starting biologic therapy were included, and underwent CS, IUS, clinical assessment and faecal calprotectin [FC] measurement at baseline and within 1 year. In addition, IUS, clinical and FC assessments were performed at week 12. The primary objective was to evaluate whether ultrasound improvement [MUC ≤ 6.2] at week 12 predicted endoscopic improvement at reassessment [MES ≤ 1]. Endoscopic remission was defined as MES = 0. RESULTS: Forty-nine patients were included [59% under infliximab, 29% under vedolizumab, 8% under adalimumab, 4% under ustekinumab]. MUC ≤ 6.2 at week 12 was the only independent predictor for MES ≤ 1 and MES = 0 at reassessment (odds ratio [OR] 5.80, p = 0.010; OR 10.41, p = 0.041; respectively). MUC ≤ 6.2 at week 12 showed a negative predictive value of 96% for detecting MES = 0. A ≥2 reduction of the MUC predicted MES = 0 (area under the curve [AUC] 0.816). MUC ≤ 4.3 was the most accurate cut-off value for MES = 0 [AUC 0.876]. Guyatt's responsiveness ratio for the MUC was 1.73 [>0.8]. CONCLUSION: MUC ≤ 6.2 at week 12 predicts long-term endoscopic response. MUC is accurate in monitoring treatment response and may be used in both clinical trials and routine practice.

Predictive value of Milan ultrasound criteria in ulcerative colitis: A prospective observational cohort study.

BACKGROUND: Endoscopic healing is an established treatment target for ulcerative colitis (UC). We have recently validated the Milan ultrasound criteria (MUC) to assess endoscopic activity in UC; a MUC score > 6.2 is a valid cut-off to discriminate endoscopic activity (Mayo endoscopic subscore > 1). OBJECTIVE: The aim of this study was to assess the predictive value of MUC on disease course in a prospective cohort of UC patients. METHODS: UC patients regardless of disease activity and current therapy, underwent colonoscopy and bowel ultrasound (US) at baseline in a blinded fashion. Correlations between baseline MUC and Mayo endoscopic subscore were assessed using Spearman's rank correlation. UC-related negative course (defined as the need for corticosteroids, or treatment escalation, or hospitalization, or need for colectomy: a composite outcome) over a median 20 months follow-up, was investigated using the Kaplan-Meier method and Cox regression analysis. RESULTS: 98 UC patients were followed up for a median time of 1.6 years (IQR 0.9¬2.7). Milan ultrasound criteria and Mayo endoscopic subscore significantly correlated at baseline (ρ = 0.653; p < 0.001). 70 patients (71%) had negative disease course during the follow-up period. Milan ultrasound criteria > 6.2 at baseline was statistically significantly associated with negative disease course (HR: 3.87, 95% CI: 2.25-6.64, p < 0.001). Kaplan-Meier analyses drawed a statistically significantly lower cumulative probability of treatment escalation, need of corticosteroids, hospitalization and colectomy, among patients who had MUC ≤ 6.2 at baseline as compared to patients with MUC > 6.2 (p < 0.05 for all outcomes). CONCLUSION: we have demonstrated for the first time the value of bowel US and an US score in predicting disease course in UC. Milan ultrasound criteria, a validated US-based score, predicts disease course in UC. Milan ultrasound criteria ≤ 6.2 may be the new treatment target to achieve to reduce the risk of worse outcomes.

JAK inhibitors in crohn's disease: ready to go?

INTRODUCTION: Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease that can lead to significant organ damage and impaired quality of life. To date, a considerable proportion of patients does not respond to biologic compounds. It is, therefore, necessary to find alternative options with adequate efficacy and safety profiles in order to increase the chances of obtaining an enduring remission of disease. Janus kinase (JAK) inhibitors are a new class of compounds that might well serve this purpose. The aim of our review is to report the available data from clinical trials testing these new drugs in patients suffering from CD. AREAS COVERED: PubMed database and ClinicalTrials.gov website were consulted in order to find the clinical trials evaluating the efficacy and safety profiles of JAK-inhibitors in CD patients, including the following compounds: tofacitinib, filgotinib, upadacitinib, TD-1473, and Pf-06651600/Pf-06700841. EXPERT OPINION: JAK-inhibitors are a promising class of oral compounds in moderate-severe CD. Further clinical trials are necessary in order to implement the available knowledge, especially on their long-term safety issues.

Bowel ultrasound score is accurate in assessing response to therapy in patients with Crohn's disease.

BACKGROUND: We developed a non-invasive bowel ultrasound score (BUSS) to assess disease activity in Crohn's disease (CD). BUSS >3.52 is an indicator of endoscopic activity (SES-CD>2). AIM: To assess whether BUSS, in addition to detecting inflammatory lesions, also detects relevant changes of these lesions over time. METHODS: This was a prospective observational study of 49 patients with active CD. All patients underwent bowel ultrasound and colonoscopy at baseline and at re-assessment after treatment with biologics and/or immunosuppressants. The primary objective was to assess the sensitivity to change of BUSS in patients treated for active CD, using the SES-CD as reference standard. RESULTS: BUSS changed significantly from baseline to re-assessment in patients achieving endoscopic response (a reduction of SES-CD of at least 50% vs baseline: 4.87 [3.78-6.0] vs 2.47 [2.25-3.36], P < 0.001) and endoscopic remission (SES-CD ≤ 2: 4.65 [3.58-6.03] vs 2.25 [2.25-3.46], P = 0.003). A change of -1.2 in BUSS over time predicted endoscopic response (AUC 0.786, 95% CI 0.645-0.890; sensitivity 74%, specificity 83%). BUSS determined endoscopic response with 80% accuracy, and endoscopic remission with 78% accuracy. BUSS accurately detected changes in lesion severity (Guyatt score: 1.41 and standardized effect score: 1.74). BUSS did not change significantly in patients who did not achieve endoscopic response (5.62 [5.26-6.15] vs 5.70 [4.97-6.19], P = 0.53) or endoscopic remission (5.62 [5.18-6.14] vs 5.10 [4.58-6.05]; P = 0.10). CONCLUSION: BUSS is sensitive to change in CD.