Long-term outcome of risankizumab in Crohn's disease: a real-world GETAID study.

INTRODUCTION: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with CD. PATIENTS AND METHODS: From May 2021 to August 2023, all consecutive CD patients treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index (HBI) <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 (10.0-18.1) months. The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174, 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174, 20.9%) were hospitalized and 22 (22/174, 12.6%) required intestinal resection. Fifty-one (29%) patients had an adverse event including 26 (15%) serious adverse events (CD flare, n=17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. Half of the patients achieved steroid-free clinical remission after one year, and the safety profile was consistent with the literature.

Risk of delayed bleeding after colorectal endoscopic submucosal dissection: the Limoges Bleeding Score.

BACKGROUND: Clinically significant delayed bleeding (CSDB) is a frequent, and sometimes severe, adverse event after colorectal endoscopic submucosal dissection (ESD). We evaluated risk factors of CSDB after colorectal ESD. METHODS: We analyzed a prospective registry of 940 colorectal ESDs performed from 2013 to 2022. The incidence of bleeding was evaluated up to 30 days. Risk factors for delayed bleeding were evaluated by multivariate logistic regression. A Korean scoring model was tested, and a new risk-scoring model was developed and internally validated. RESULTS: CSDB occurred in 75 patients (8.0%). The Korean score performed poorly in our cohort, with a receiver operating characteristic (ROC) curve of 0.567. In the multivariate analysis, risk factors were age ≥75 years (odds ratio [OR] 1.63; 95%CI 0.97-2.73; 1 point), use of antithrombotics (OR 1.72; 95%CI 1.01-2.94; 1 point), rectal location (OR 1.51; 95%CI 0.92-2.48; 1 point), size >50 mm (OR 3.67; 95%CI 2.02-7.14; 3 points), and American Society of Anesthesiologists (ASA) score of III or IV (OR 2.26; 95%CI 1.32-3.92; 2 points). The model showed fair calibration and good discrimination, with an area under the ROC curve of 0.751 (95%CI 0.690-0.812). The score was used to define two groups of patients, those with low-medium risk (0 to 4 points) and high risk (5 to 8 points) for CSDB (respective bleeding rates 4.1% and 17.5%). CONCLUSION: A score based on five simple and meaningful variables was predictive of CSDB.

Prevalence and clinical significance of the muscle retracting sign during endoscopic submucosal dissection of large macronodular colorectal lesions (with videos).

BACKGROUND AND AIMS: The muscle retracting sign (MRS) can be present during endoscopic submucosal dissection (ESD) of macronodular colorectal lesions. The prevalence of MRS and its pathologic and clinical implications is unclear. This study evaluated the effect of MRS on the technical and clinical outcomes of ESD. METHODS: All patients referred for ESD of protruding lesions or granular mixed lesions with >10 mm macronodule granular mixed laterally spreading tumors (LST-GMs) in 2 academic centers from January 2017 to October 2022 were prospectively included. Size of the macronodule was analyzed retrospectively. The primary outcome was the curative resection rate according to MRS status. Secondary outcomes were R0 resection, perforation, secondary surgery rate, and risk factors for MRS. RESULTS: Of 694 lesions, 84 (12%) had MRS (MRS+). The curative resection rate was decreased by MRS (MRS+ 41.6% vs lesions without MRS [MRS-] 81.3%), whereas the perforation (MRS+ 22.6% vs MRS- 9.2%), submucosal cancer (MRS+ 34.9% vs MRS- 9.2%), and surgery (MRS+ 45.2% vs MRS- 6%) rates were increased. The R0 resection rate of MRS+ colonic lesions was lower than that of rectal lesions (53% vs 74.3%). In multivariate analysis, protruding lesions (odds ratio, 2.47; 95% confidence interval, 1.27-4.80) and macronodules >4 cm (odds ratio, 4.24; 95% confidence interval, 2.23-8.05) were risk factors for MRS. CONCLUSIONS: MRS reduces oncologic outcomes and increases the perforation rate. Consequently, procedures in the colon should be stopped if MRS is detected, and those in the rectum should be continued due to the morbidity of alternative therapy.

Risk factors for stent dysfunction during long-term follow-up after EUS-guided biliary drainage using lumen-apposing metal stents: A prospective study.

Background: EUS-guided choledoco-duodenostomy using electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) is becoming the gold standard in case of endoscopic retrograde cholangio-pancreatography failure for distal malignant obstruction. Long-term data in larger samples are lacking. Methods: This was a prospective monocentric study including all patients who underwent EUS-guided choledochoduodenostomy (CDS) between September 2016 and December 2021. The primary endpoint was the rate of biliary obstruction during follow-up. Secondary endpoints were technical and clinical success rates, adverse event rates, and identification of risk factors for biliary obstruction. Results: One hundred and twenty-three EUS-guided CDS using ECE-LAMS were performed at Limoges University Hospital were performed during the study period and included in the study. The main cause of obstruction was pancreatic adenocarcinoma in 91 (74.5%) cases. The technical and clinical success rates were 97.5% and 91%, respectively. Twenty patients (16.3%) suffered from biliary obstructions during a mean follow-up of 242 days. The clinical success rate for endoscopic desobstruction was 80% (16/20). In uni- and multivariate analyses, only the presence of a duodenal stent (odds ratio [OR]: 3.6, 95% confidence interval [CI] 95%: 1.2-10.2; P = 0.018) and a bile duct thinner than 15 mm (OR: 3.9, CI 95%: 1.3-11.7; P = 0.015) were the significant risk factors for biliary obstruction during the follow-up. Conclusion: Obstruction of LAMS occurred in 16.3% of cases during follow-up and endoscopic desobstruction is efficacious in 80% of cases. The presence of duodenal stent and a bile duct thinner than 15 mm are the risk factors of obstruction. Except in these situation, EUS-CDS with ECE-LAMS could be proposed in the first intent in case of distal malignant obstruction.

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. METHODS: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included clinical response (≥3-point decrease of HB score and/or (HB) score <5), biochemical remission (CRP ≤ 5 mg/L), need for CD-related surgery and adverse events. RESULTS: Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had a previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. In subgroup analysis restricted to patients with objective signs of inflammation at baseline (n = 79), steroid-free clinical remission at week 12 was observed in 39.2% of patients. Biochemical remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalisation was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (odds ratio (OR), 2.80; 95% CI: 1.07-7.82; p = 0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. CONCLUSION: In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided a clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

Gastric peroral endoscopic myotomy in refractory gastroparesis: long-term outcomes and predictive score to improve patient selection.

BACKGROUND AND AIMS: Limited data exist concerning the long-term efficiency of gastric peroral endoscopic myotomy (G-POEM) as a treatment of refractory gastroparesis. This study evaluated the 3-year results of G-POEM in patients with refractory gastroparesis. METHODS: This was a prospective multicenter study of all G-POEM operations performed in 2 expert French centers for 46 patients with refractory gastroparesis with at least 3 years of follow-up. RESULTS: Clinical success was 65.2% at 36 months. There was significant improvement in symptom severity. Median Gastroparesis Cardinal Symptom Index decreased from 3.33 to 1.80 (P < .0001), with improvement in all subscales. We created a predictive score concerning G-POEM success (G-POEM predictive score) to which points were assigned as follows: nausea subscale <2: predictive of success, 1 point; satiety subscale >4: predictive of success, 1 point; bloating subscale >3.5: predictive of success, 1 point; percentage of gastric retention at 4 hours on scintigraphy >50%: 1 point. A threshold of 2 was identified by receiver operating characteristic curve analysis with an area under the curve of .825 that predicted clinical success with a sensitivity of 93.3% (95% confidence interval [CI], .77-.99), specificity of 56.3% (95% CI, .33-.77), positive predictive value of 80% (95% CI, .67-.93), negative predictive value of 81.8% (95% CI, .59-1.00), and accuracy of 80.4% (95% CI, .69-.92). Patients with a score ≥2 were significantly more likely to be responders at 3 years than were patients with a score <2 (80% and 18%, respectively; P = .0004). CONCLUSIONS: The clinical success of G-POEM for refractory gastroparesis was 65.2% at 36 months. Our predictive score offers an easy tool that needs to be confirmed in other studies.

The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment classification for identification of large laterally spreading lesions lacking submucosal carcinomas: A prospective study of 663 lesions.

INTRODUCTION: Optical diagnosis is necessary when selecting the resection modality for large superficial colorectal lesions. The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment (CONECCT) encompasses overt (irregular pit or vascular pattern) and covert (macroscopic features) signs of carcinoma in an all-in-one classification using validated criteria. The CONECCT IIC subtype corresponds to adenomas with a high risk of superficial carcinoma that should be resected en bloc with free margins. METHODS: This prospective multicentre study investigated the diagnostic accuracy of the CONECCT classification for predicting submucosal invasion in colorectal lesions >20 mm. Optical diagnosis before en bloc resection by endoscopic submucosal dissection (ESD) was compared with the final histological diagnosis. Diagnostic accuracy for the CONECCT IIC subtype was compared with literature-validated features of concern considered to be risk factors for submucosal invasion (non-granular large spreading tumour [NG LST], macronodule >1 cm, SANO IIIA area, and Paris 0-IIC area). RESULTS: Six hundred 63 lesions removed by ESD were assessed. The en bloc, R0, and curative resection rates were respectively 96%, 85%, and 81%. The CONECCT classification had a sensitivity (Se) of 100%, specificity (Sp) of 26.2%, positive predictive value of 11.6%, and negative predictive value (NPV) of 100% for predicting at least submucosal adenocarcinoma. The sensitivity of CONECCT IIC (100%) to predict submucosal cancer was superior to all other criteria evaluated. COlorectal NEoplasia Endoscopic Classification to Choose the Treatment IIC lesions constituted 11.5% of all submucosal carcinomas. CONCLUSION: The CONECCT classification, which combines covert and overt signs of carcinoma, identifies with very perfect sensitivity (Se 100%, NPV 100%) the 30% of low-risk adenomas in large laterally spreading lesions treatable by piecemeal endoscopic mucosal resection or ESD according to expertise without undertreatment. However, the low specificity of CONECCT leads to a large number of potentially not indicated ESDs for suspected high-risk lesions.

Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer.

OBJECTIVE: Endoscopic submucosal dissection (ESD) in a curative intent for submucosa-invasive early (T1) colorectal cancers (T1-CRCs) often leads to subsequent surgical resection in case of histologic parameters indicating higher risk of nodal involvement. In some cases, however, the expected benefit may be offset by the surgical risks, suggesting a more conservative approach. DESIGN: Retrospective analysis of consecutive patients with T1-CRC who underwent ESD at 13 centres ending inclusion in 2019 (n=3373). Cases with high risk of nodal involvement (non-curative ESD: G3, submucosal invasion>1000 µm, lymphovascular involvement, budding or incomplete resection/R1) were analysed if follow-up data (endoscopy/imaging) were available, regardless of the postendoscopic management (follow-up vs surgery) selected by the multidisciplinary teams in these institutions. Comorbidities were classified according to Charlson Comorbidity Index (CCI). Outcomes were disease recurrence, death and disease-related death rates in the two groups. Rate of residual disease (RD) at both the previous resection site and regional lymph nodes was assessed in the surgical cases as well as from follow-up in the follow-up group. RESULTS: Of 604 patients treated by colorectal ESD for submucosally invasive cancer, 207 non-curative resections (34.3%) were included (138 male; mean age 67.6±10.9 years); in 65.2% of cases, no complete resection was achieved (R1). Of the 207 cases, 60.9% (n=126; median CCI: 3; IQR: 2-4) underwent surgical treatment with RD in 19.8% (25/126), while 39.1% (n=81, median CCI: 5; IQR: 4-6) were followed up by endoscopy in all cases. Patients in the follow-up group had a higher overall mortality (HR=3.95) due to non-CRC causes (n=9, mean survival after ESD 23.7±13.7 months). During this follow-up time, tumour recurrence and disease-specific survival rates were not different between the groups (median follow-up 30 months; range: 6-105). CONCLUSION: Following ESD for a lesion at high risk of RD, follow-up only may be a reasonable choice in patients at high risk for surgery. Also, endoscopic resection quality should be improved. TRIAL REGISTRATION NUMBER: NCT03987828.