Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a frequently employed procedure for diagnosing and treating pancreaticobiliary diseases. The selection of an appropriate sedative agent is crucial for ensuring patient comfort and procedural success. An optimal sedative should offer a predictable duration of action and a high safety profile. This study aimed to compare the efficacy and safety of remimazolam and propofol in patients undergoing ERCP procedures.

Aims & Methods

A randomized, single-blind, single center study was conducted comparing remimazolam and propofol for inpatient ERCP sedation. The study medications were administered under the supervision of the endoscopist. A total of 110 patients scheduled for ERCP were randomly assigned to receive either remimazolam or propofol. The primary endpoint was a composite of successful procedure completion and no requirement for rescue medication. Secondary endpoints included sedation efficacy, recovery time, and adverse events.

Results

Of the 110 patients randomized, 108 underwent sedation and ERCP (53 received remimazolam, 55 propofol). The primary endpoint was achieved for 100% of patients in both groups. The incidence and frequency of treatment-emergent adverse events, including desaturation, were comparable between the two groups. ERCP initiation occurred sooner in the propofol group (mean, 63.18 ± 16.56 seconds) compared to the remimazolam group (75.23 ± 32.27 seconds; p-value=0.02). Additionally, the time to full alertness after ERCP completion was significantly shorter in the propofol group than the remimazolam group (304.18 ± 146.25 vs. 448.34 ± 224.09 seconds; p-value<0.001).

Conclusion

This trial demonstrated non-inferiority of remimazolam to propofol in achieving the primary endpoint of successful ERCP completion without the need for rescue medication. The incidence and frequency of adverse events were comparable between the two groups. However, our study also revealed that propofol had a faster onset and recovery time compared to remimazolam. Although this difference may not be clinically significant, it could have practical implications in certain cases. Consequently, remimazolam can be considered a safe and effective alternative to propofol for ERCP sedation, potentially expanding clinicians’ options and improving patient outcomes. Further research is warranted to determine the optimal choice of sedative agents for various patient populations and procedures.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for Crohn's disease (CD), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate/loss of response. Factors associated with VDZ dose escalation from Q8W to Q4W and real-world outcomes remain underexplored.

Aims & Methods

Adults with moderate to severe CD initiating VDZ Q8W maintenance therapy were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance therapy any time after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without dose escalation (Q8W maintenance). Baseline characteristics were summarized as median (range) and frequency (%) and compared between cohorts. Rates of clinical remission (Harvey-Bradshaw Index [HBI]<5) were described stratifying by prior biologic experience. Associations between baseline factors and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after treatment initiation and dose escalation were evaluated in the Q8W>Q4W cohort using Kaplan-Meier survival analysis.

Results

250 patients were included in the Q8W>Q4W maintenance cohort (39% bio-naïve), and 116 in the Q8W maintenance cohort (51% bio-naïve). In both cohorts, median age at treatment initiation was 50 years and baseline HBI score was 10. In the Q8W>Q4W maintenance cohort, median disease duration prior to initiation of treatment was 14 years (0-69) and median follow-up duration was 22 months (7-60). In the Q8W cohort, median disease and follow-up duration were 8 years (0-50) and 35 months (27-46), respectively. At 14 weeks post-treatment initiation, rates of remission in the Q8W>Q4W maintenance cohort were 47% (bio-naïve) and 22% (bio-experienced), and in the Q8W cohort 61% (bio-naïve) and 48% (bio-experienced) (Table 1). Among patients in the Q8W>Q4W maintenance cohort not in remission at the time of dose escalating, 33% achieved remission 3 months after dose escalation to Q4W. Disease duration at baseline was shorter in these patients than in those who did not achieve remission (8 months [0-52] vs. 16 months [0-69], p=0.007). In the Q8W>Q4W maintenance cohort, 12- and 24-month treatment persistence after treatment initiation was 91% and 64% (bio-naïve) and 94% and 67% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 66% and 59% (bio-naïve) and 69% and 53% (bio-experienced) (Table 1).

Conclusion

Patients with CD who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of clinical remission than those remaining on Q8W treatment, and one third achieved clinical remission 3 months after dose escalating. Baseline disease duration was significantly associated with remission among those escalating to Q4W.

References

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Disclosure

AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda. AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Ulcerative colitis (UC) has increasingly been recognized as a progressive disease. However, the benefit of starting early biologic therapy (BT) has not been established, contrary to Crohn´s disease. We aimed to assess if early intervention improves UC outcomes, particularly in preventing disease progression.

Aims & Methods

We conducted a retrospective multicenter study (11 centers) including adult UC patients who initiated BT until 2019 (minimum follow-up [FU]: 5 years). Early intervention was defined as BT initiation within ≤12 months of diagnosis. The primary outcome was UC progression at 5 and 10 years, defined as a composite of proximal extension, colonic structural changes (stenosis/ tubularization) and dysplasia/cancer. Secondary outcomes included clinical endpoints: hospitalizations, colectomy and corticosteroid use. Multivariate analysis was performed, adjusted for disease severity, extent, and prior activity.

Results

A total of 236 patients were included, with 28.8% (n=68) initiating BT within ≤12 months (mean FU after BT initiation: 8.06 ± 4.12 years).
Early intervention was associated with a reduced risk of proximal extension after BT initiation (p=0.012). In multivariable Cox regression, later BT initiation was an independent predictor of colonic structural changes at 10 years (HR 8.54; 95% CI 1.15-62.63; p=0.036). Later BT initiation independently predicted the composite outcome of progression (23.2% vs 5.9%) at 5 years (HR 5.97; 95% CI 1.42-25.13; p=0.015) and 10 years (HR 4.58; 95% CI 1.41-14.88; p=0.011). No differences in clinical outcomes were observed.
Longer disease activity before BT was also a predictor of the primary outcome at 5 years (HR 4.20; 95% CI 1.27–13.82; p=0.018) and 10 years (HR 3.60; 95% CI 1.28–10.12; p=0.015).

Conclusion

Starting BT early in the disease course may reduce the long-term risk of disease progression, reshaping the window of opportunity in UC.

References

Lujan, Rona, et al. "Early initiation of biologics and disease outcomes in adults and children with inflammatory bowel diseases: results from the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort." Gastroenterology 166.5 (2024): 815-825.

Introduction

Diverticulosis was once regarded as an uncommon anatomic variant with different types of complication, Faecal calprotectin (FC) is a cytoplasmic antimicrobial
compound prominent in granulocytes, monocytes, and macrophages (1).

Aims & Methods

we aim to assess the fecal calprotectin values in colonic diferticulosis as a non invasive marker of disease severity.

Results

We enrolled in this study 360 consecutive patients who had undergone a total colonoscopy and MSCT on Abdomen and complete laboratory investigation including fecal calportectin, Age was distributed as 46.61±11.57 with minimum 15 and maximum 80 years and regard sex distribution female were majority with 59.7% fecal calportectin significantly positive correlated with CRP, NIS and Hinchey classification. Mild diverticulosis showed Significant area under curve with cutoff >65 and with sensitivity 97.0%and specificity 82.8%. moderate diverticuosis showed Significant area under curve with cutoff >162 <175 and with sensitivity 83.3%and specificity 96.0%. Severe Significant area under curve with cutoff >175 and with sensitivity 85.0%and specificity 92.5%.

Conclusion

Faecal calprotectin (FC) is inflammatory marker considered as a stronger predictor of diverticulosis diseases in Non IBD Patients.

References

(1) Roseth AG, Fagerhol M, Aadland E, Schjonsby H (1992) Assessment of neutrophil dominating protein calprotectin in feces. A methodological study. Scand J Gastroenterol 27:793–798