External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.

OBJECTIVE: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy). DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively). CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal. TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.

Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID.

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

A comparison of target volumes drawn on arterial and venous phase scans during radiation therapy planning for patients with pancreatic cancer: the PANCRINJ study.

BACKGROUND: The planification of radiation therapy (RT) for pancreatic cancer (PC) requires a dosimetric computed tomography (CT) scan to define the gross tumor volume (GTV). The main objective of this study was to compare the inter-observer variability in RT planning between the arterial and the venous phases following intravenous contrast. METHODS: PANCRINJ was a prospective monocentric study that included twenty patients with non-metastatic PC. Patients underwent a pre-therapeutic CT scan at the arterial and venous phases. The delineation of the GTV was performed by one radiologist (gold standard) and two senior radiation oncologists (operators). The primary objective was to compare the Jaccard conformity index (JCI) for the GTVs computed between the GS (gold standard) and the operators between the arterial and the venous phases with a Wilcoxon signed rank test for paired samples. The secondary endpoints were the geographical miss index (GMI), the kappa index, the intra-operator variability, and the dose-volume histograms between the arterial and venous phases. RESULTS: The median JCI for the arterial and venous phases were 0.50 (range, 0.17-0.64) and 0.41 (range, 0.23-0.61) (p = 0.10) respectively. The median GS-GTV was statistically significantly smaller compared to the operators at the arterial (p < 0.0001) and venous phases (p < 0.001), respectively. The GMI were low with few tumors missed for all patients with a median GMI of 0.07 (range, 0-0.79) and 0.05 (range, 0-0.39) at the arterial and venous phases, respectively (p = 0.15). There was a moderate agreement between the radiation oncologists with a median kappa index of 0.52 (range 0.38-0.57) on the arterial phase, and 0.52 (range 0.36-0.57) on the venous phase (p = 0.08). The intra-observer variability for GTV delineation was lower at the venous phase than at the arterial phase for the two operators. There was no significant difference between the arterial and the venous phases regarding the dose-volume histogram for the operators. CONCLUSIONS: Our results showed inter- and intra-observer variability in delineating GTV for PC without significant differences between the arterial and the venous phases. The use of both phases should be encouraged. Our findings suggest the need to provide training for radiation oncologists in pancreatic imaging and to collaborate within a multidisciplinary team.

Real-world comparison of the effectiveness between ustekinumab and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent.

BACKGROUND: Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis (UC) but head-to-head trials are lacking. AIM: We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-TNF failure in UC patients. PATIENTS AND METHODS: In this multicenter study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting). RESULTS: Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity-score analysis, steroid-free clinical remission (SFCR) (Mayo score partial ≤ 2) was achieved at week 16 in 38.0% and 40.3%, of patients treated with vedolizumab and ustekinumab, respectively (aOR = 1.11 [0.39-3.13], p = 0.85). Rate of SFCR in patients exposed to one line, 2 lines and 3 lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% (p=0.52), 44.4% vs 33.8% (p=0.52) and 2.6% vs 19.1% (p=0.027). Endoscopic remission (SFCR and endoscopic Mayo score ≤1) and histological remission (SFCR, endoscopic remission and Nancy histological index ≤1) at W16 were achieved in respectively, 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p=0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p=0.012) in vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) were observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR=0.31, 95%CI [0.11-0.82], p=0.018) was significantly associated with decreased rate of SFCR among patients treated with ustekinumab. CONCLUSION: While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab to induce endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Long-term Outcome of Risankizumab in Crohn's Disease: a Real-world GETAID Study.

BACKGROUND & AIMS: 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 Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD 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 months (interquartile range, 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 patients (29%) 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. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Long-term outcomes of endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction.

BACKGROUND: Hepaticogastrostomy drainage through endoscopic ultrasound (EUS-HGS) has emerged in the 2010s as a new technique for biliary decompression in cases of endoscopic retrograde cholangiopancreatography (ERCP) failure for malignant biliary obstruction (MBO). Substantial technical and procedural progress in performing EUS-HGS has been achieved, allowing high technical and clinical success and an acceptable risk of adverse events in studies mainly focusing on short-term outcomes. However, the long-term effects of EUS-HGS and the risk of recurrent biliary obstruction (RBO) have not been fully evaluated. OBJECTIVES: To evaluate the long-term effects of EUS-HGS and the risk of RBO. METHODS: Data from 211 patients undergoing technically successful EUS-HGS in three academic centers were retrospectively collected. Clinical success, adverse events, RBO, and reinterventions were evaluated. RESULTS: In total, 198 patients underwent technically successful EUS-HGS for MBO. The median overall survival was 144 days [108, 2011] after the procedure. Mean patient age was 69.39 (12.91) years. The cause of MBO was pancreatic cancer (n = 98, 49.5%) followed by cholangiocarcinoma (n = 29, 14.6%). The location of MBO was distal in 27.6% of cases and proximal in 68.4%. Adverse events were observed during the follow-up in 65 patients (33%). On multivariate analysis, the use of partially covered self-expandable metal stents (PCSEMS) was associated with a lower risk of RBO (HR = 0.47 [0.24-0.95], p = 0.034). Additionally, patients with distal stenoses had a trend toward better stent patency (HR = 0.06[0-0.77], p = 0.031). RBO developed in 38 cases (19.1%) mainly due tumor ingrowth (36.8%) with a high success rate of endoscopic management. CONCLUSIONS: While RBO occurred in a notable proportion of patients, the primary cause of mortality was progression of the underlying malignancy rather than stent dysfunction. The efficiency of stents, particularly PCSEMS, and the high success rate of endoscopic management for RBO underscore the effectiveness and reliability of these treatments in managing biliary complications.