Exabis Library

Background

Endoscopic remission is associated with better outcomes in ulcerative colitis (UC). However, colonoscopy (CS) is invasive and poorly tolerated by patients. Recently, we developed and externally validated non-invasive ultrasonography based criteria [Milan ultrasound criteria (MUC)] to assess and grade endoscopic activity in UC. We also confirmed that a MUC score > 6.2 is a valid cut-off to discriminate endoscopic activity, defined by a Mayo endoscopic subscore > 2.
Aim of this study was to assess the predictive role of MUC on disease course in a prospective cohort of UC patients.

Methods

UC consecutive patients were followed for at least 12 months after performing baseline bowel US. UC-related outcomes, including need of treatment escalation (defined as the need of corticosteroids or change/optimization of immunosuppressants), hospitalization and surgery, were assessed at 1 year by logistic regression analysis, and were analyzed after long term follow-up (5 years) using Kaplan-Meier survival analysis.

Results

87 UC consecutive patients were included in the study, 31 (36%) were in endoscopic remission (Mayo endoscopic subscore 0-1) and 56 (64%) in endoscopic activity (Mayo endoscopic subscore 2-3). MUC and Mayo endoscopic subscore significantly correlated at baseline (Spearman’s rank correlations [rho]= 0.642; 95% confidence interval (CI) 0.499 to 0.751; p < 0.001). The multivariable analysis identified as independent predictors of need of treatment escalation throughout the 12-month period as being: MUC > 6.2 (OR: 5.95, 95% CI: 1.32–26.76, p < 0.020) and a partial Mayo score (PMS) > 2 (OR: 26.88, 95% CI: 5.01–144.07, p < 0.001). Kaplan-Meier survival analysis of long-term follow up demonstrated a lower cumulative probability of need for surgery and hospitalization in patients with MUC < 6.2 compared to MUC > 6.2 (Fig. 1A and 1B), as well as in patients with a Mayo endoscopic subscore of < 1 compared to Mayo endoscopic subscore of 2-3 (Fig. 1C and 1D).

Conclusion

MUC is a novel non invasive tool that predicts the course of UC in the short and long term follow-up. 

Fatigue is one of the most common symptoms in IBD resulting in decreased quality of life, impaired work productivity, and higher societal costs. However, little is known about its etiology and pathophysiology. We aimed to estimate the prevalence of fatigue and to identify predictive factors for fatigue.

The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites. 1946 (74%) patients completed the baseline questionnaires. We assessed the prevalence of fatigue at baseline using a single item from the IBD Control questionnaire. To identify predictors for fatigue, we performed univariable and multivariable analyses including demographic, biochemical, environmental and psychosocial factors such as anxiety and depression [HADS], sleep quality [PSQI] and physical exercise [GPAQ]).

759/1919 IBD patients in clinical remission (39.6%) reported fatigue in the past 2 weeks, while 1034 patients (53.9%) did not report fatigue. Patients who reported fatigue were more frequently female, had more frequently CD, and were more frequently smokers (Table 1). Univariable comparisons showed higher inflammatory markers in the fatigued group, with fewer patients in clinical remission. Multivariable analyses identified female sex (OR 2.4), CRP>5 (OR 2.1), bad sleep quality (OR 2.5), anxiety (OR 1.8) and depression (OR 6.2) as independent factors associated with fatigue (Table 2).

Table 1

We show the significant burden of fatigue in IBD patients and describe putative causes which demonstrate both the impact of residual gut inflammation and the relationship between fatigue and psychological well-being. The impact of environmental and dietary factors on fatigue is being further investigated with ongoing longitudinal data collection in the PREdiCCt study.

Upadacitinib (UPA) is a selective and reversible Janus kinase inhibitor.U-ACCOMPLISH is one of two phase 3 induction trials that evaluated the safety and efficacy of UPA 45 mg once daily (QD) in adults with ulcerative colitis (UC).

U-ACCOMPLISH was a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026) that enrolled patients with moderate-to-severe UC (defined as adapted Mayo score 5–9 with centrally read endoscopic score 2–3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Patients were randomized 2:1 to UPA 45 mg QD or placebo (PBO) for 8 weeks. At week 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA 45 mg QD for additional 8 weeks.The primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic– histologic evaluations from the 8-week PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.

522 patients were randomized (UPA, n=345; PBO, n=177);the intent-to-treat population included 341 patients in UPA and 174 patients in PBO group. Baseline demographics and disease characteristics were similar between groups; 50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of patients receiving UPA 45 mg QD (33.5%) versus PBO (4.1%) achieved the primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7]; P<0.001). A significantly higher proportion of patients receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001; Figure 1).Serious adverse events were reported by 3.2% and 4.5% of patients in UPA and PBO groups, respectively (Table 2). Similar rates of serious infection were observed in both groups (0.6%); 2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported in the study. One patient with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 patient with gastrointestinal perforation were reported in the placebo group.

In U-ACCOMPLISH, 8-week UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints.The treatment was well tolerated, and the safety profile and AE prevalence was comparable with previous studies of UPA with no new safety signals identified.