Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study.

BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Health Literacy and Quality of Life in Young Adults From The Belgian Crohn's Disease Registry Compared to Type 1 Diabetes Mellitus.

Background and Aims: The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control. Methods: In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13-16), problematic (9-12) or inadequate (0-8). QoL was dichotomized into "no problems" (EQ-5D level 1) or "problems" (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney U) analyses and Spearman correlations were performed. Results: A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM (p = 0.6) with similar proportions of sufficient (60 vs. 68%, p = 0.4), problematic (34 vs. 26%, p = 0.3) and inadequate HL (both 6%, p = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, p =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, p = 0.06). HL and QoL correlated in CD (r = 0.6, p < 0.001) and DM patients (r = 0.6, p < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, p = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], p = 0.04) compared to those without. Conclusions: Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.

Solute carrier family 12 member 2 as a proteomic and histological biomarker of dysplasia and neoplasia in ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.

Evaluation of the efficacy of octreotide LAR in the treatment of Crohn's disease associated refractory diarrhea.

OBJECTIVES: Diarrhea is one of the main symptoms of Crohn's disease (CD). It is usually significantly improved with specific CD treatments, loperamide or cholestyramine. However, in some cases, diarrhea becomes refractory. The aim of this study was to assess the safety and efficacy of octreotide in this situation. MATERIALS AND METHODS: Fifteen patients with CD refractory diarrhea defined by at least an average of five smooth or liquid stools per day despite an optimized CD treatment were included from three Belgian centers. Two patients were lost to follow-up. A subcutaneous injection of 100 µg octreotide was performed three times a day during three days. When the drug had been well tolerated, an intramuscular injection of 30 mg octreotide (Sandostatin® LAR 30) was realized. Evaluation was done at day 31. The primary endpoint was to assess the effect on the mean number of smooth or liquid stools per day. RESULTS: A significant reduction (p = 0.0001) of the average number of smooth or liquid stools over the last seven days was observed between baseline and day 31. The maximum number of smooth or liquid stools also significantly decreased (p = 0.0009). Four patients (26.7%) presented mild nonspecific adverse events but no serious one. We also observed a significant decrease (p = 0.0006) of the Harvey-Bradshaw Index (HBI) and a significant improvement (p = 0.0012) of the inflammatory bowel disease questionnaire (IBDQ). CONCLUSIONS: In this uncontrolled open-label study, octreotide appeared safe and effective in CD refractory diarrhea, in addition to CD treatments. It significantly improved the number of liquid or smooth stools, the HBI and the IBDQ.

Noninvasive assessment of Crohn's disease intestinal lesions with (18)F-FDG PET/CT.

UNLABELLED: Pilot studies have shown good sensitivity and specificity for (18)F-FDG PET in detecting gastrointestinal lesions of Crohn's disease. The combination of (18)F-FDG PET with CT may further improve the localization and characterization of lesions with increased (18)F-FDG uptake. Our aim was to assess the use of (18)F-FDG PET/CT in evaluating the activity and location of Crohn's disease along the gastrointestinal tract. METHODS: After giving informed consent, 22 patients with Crohn's disease were prospectively studied. They underwent (18)F-FDG PET/CT, followed by ileocolonoscopy within 1 wk (mean, 2 d). The Crohn's disease activity index (CDAI) was calculated, and serum C-reactive protein (CRP) and fecal calprotectin were measured before endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) was calculated during endoscopy. The global CDEIS score and endoscopic subscores for various ileocolonic segments were used for analysis. RESULTS: Globally, 95 intestinal and colonic segments in 22 patients were analyzed. (18)F-FDG PET/CT detected 35 of 48 endoscopically affected segments (sensitivity for the detection of endoscopic lesions, 72.9%). The sensitivity of (18)F-FDG PET/CT for the detection of severe endoscopic lesions (deep ulcers and strictures) was 100% (14/14). The global PET/CT score significantly correlated with CDEIS (r = 0.51; 95% confidence interval [CI], 0.09-0.77; P = 0.017), CDAI (r = 0.58; 95% CI, 0.17-0.80; P = 0.005), and CRP (r = 0.56; 95% CI, 0.19-0.81; P = 0.007). CONCLUSION: (18)F-FDG PET/CT was globally well correlated to the clinical, endoscopic, and biologic activity of Crohn's disease. Above all, this technique had a good sensitivity for the detection of intestinal and colonic segments with moderate to severe mucosal lesions. The potential impact of this promising tool on the global management of patients with Crohn's disease should be further evaluated in prospective studies.