Introduction

Post-operative recurrence (POR) affects a substantial proportion of Crohn's disease (CD) patients following intestinal resection. While ileocolonoscopy remains the gold standard for detecting recurrence, its invasive nature and patient burden have spurred interest in non-invasive monitoring approaches. This study evaluates the performance of faecal calprotectin (FC) and cross-sectional imaging at different timepoints in predicting endoscopic recurrence in postoperative CD patients.

Aims & Methods

In this multicenter retrospective cohort of 895 CD patients who underwent ileocecal resection, we analyzed the diagnostic accuracy of FC measurements at 3, 6-12, and 18-24 months postoperatively for predicting endoscopic recurrence (Rutgeerts score ≥i2 or SES-CD ≥3). Additionally, we assessed the concordance between intestinal ultrasound (IUS) and magnetic resonance imagings (MRI) and endoscopic findings at both 6-12- and 18-24-months using kappa statistics.

Results

FC demonstrated modest discriminatory ability at 3 months (AUC 0.642, 95% CI: 0.530-0.753) and 6-12 months (AUC 0.653, 95% CI: 0.593-0.713), with improved performance at 18-24 months (AUC 0.676, 95% CI: 0.608-0.744). The optimal cutoff values for FC (47.5 μg/g at 3 and 6-12 months; 80.0 μg/g at 18-24 months) were substantially lower than standard thresholds (150-250 μg/g) used in non-operated patients.
At 6-12 months, radiological and endoscopic assessments showed moderate agreement (κ=0.426, p<0.001) with 63.2% concordance. At 18-24 months, IUS demonstrated superior agreement with endoscopic findings (κ=0.531, p<0.001; sensitivity 83.8%, specificity 72.7%) compared to MRI (κ=0.324, p<0.001). Notably, radiological remission at 18-24 months was identified as a significant protective factor against surgical recurrence (OR 0.356, 95% CI: 0.179-0.705, p=0.003).

Table I: Concordance between endoscopic and radiologic findings (IUS and MRI) for inflammation and remission at 18–24 months post-ileocecal resection. Abbreviations: IUS: Intestinal ultrasound, MRI: Magnetic resonance imaging.

Conclusion

Non-invasive monitoring with FC shows promise in postoperative CD surveillance, though diagnostic thresholds differ substantially from those established for non-operated patients. IUS demonstrates superior concordance with endoscopic findings compared to MRI, particularly at later timepoints. The protective role of radiological remission against surgical recurrence highlights the importance of transmural healing. Combining FC with radiological assessment, especially IUS, may provide a comprehensive, patient-friendly approach to monitoring postoperative CD, potentially reducing the need for invasive procedures in selected patients but further studies are needed in this direction.

Introduction

Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies suggest a beneficiary effect for appendectomy in inducing and maintaining remission. Therefore, appendectomy might be considered as an alternative treatment in these patients.

Aims & Methods

Aim: To evaluate the efficacy of appendectomy in maintaining remission in UC patients.
Methods: Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score <3 with endoscopic subscore of 0 or 1) after being medically treated for disease relapse within 12 months prior to randomization were enrolled in the Netherlands and United Kingdom. Patients were randomized (1:1) to undergo additional appendectomy (intervention group) or continue current medical therapy (control group). The primary outcome was the one-year UC relapse rate, defined as a total Mayo-score score ≥5 with endoscopic subscore of 2 or 3. To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed. Trial progress and safety reports with accumulated number of (serious) adverse events in both groups were presented to the Data Safety Monitoring Board (DSMB) annually, and therefore data are available. Last patient was included in August 2022, so the final analyses will commence in September 2023.

Results

Between September 2012 and September 2022, 198 patients were randomized. A total of 99 patients were included in the intervention group and 99 patients in the control group. The one-year follow-up data were complete for 183 patients in April 2023.
There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having been treated for either proctitis (38.9%) or left sided colitis (35.9%) (Table 1). A total of three serious adverse events (SAE) were reported in the appendectomy group, of which two were related to the surgical procedure (reintervention for mechanical ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). During follow up there were no colectomies in the appendectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group. In addition, the one-year reported colitis-associated adverse event rate was significantly lower in the appendectomy group when compared to the control group (43.4% vs. 62.7%, P=0.01).

Conclusion

Appendectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events significantly. This suggests that the final analysis of the primary outcome parameter (relapse rate) in September 2023 could demonstrate that appendectomy is superior to standard medical therapy alone in maintaining remission in these patients.

Introduction

Upadacitinib (UPA) is an oral, reversible Janus kinase (JAK) inhibitor that recently demonstrated efficacy compared with placebo (PBO) in 2 double-blind, multicenter induction studies, U-EXCEED (NCT03345836) and U-EXCEL (NCT01205776), and in a pre-specified primary analysis of 502 patients in the phase 3 maintenance study U-ENDURE (NCT03345823).^1-3 UPA is approved for the treatment of moderately to severely active Crohn’s disease (CD).^4,5 The current analysis evaluated the efficacy and safety of UPA in the full intent-to-treat maintenance population of U-ENDURE.

Aims & Methods

After 12 weeks of induction therapy, clinical responders (patients who achieved ≥ 30% decrease in average daily very soft/liquid stool frequency [SF] and/or ≥ 30% decrease in average daily abdominal pain score [APS] and both not worse than baseline) to UPA 45 mg were re‑randomized to 52 weeks of maintenance therapy with UPA 30 mg (UPA30), UPA 15 mg (UPA15), or placebo (PBO) once daily. Efficacy outcomes, including clinical remission per SF/APS, clinical remission per CD Activity Index (CDAI), endoscopic response, maintenance of clinical remission, clinical response per CDAI (CR-100), endoscopic remission, steroid-free clinical remission, and deep remission (clinical remission combined with endoscopic remission) were assessed through 52 weeks. Safety during U-ENDURE was documented. The efficacy analysis included all patients who were randomized and received ≥ 1 dose of study drug in U‑ENDURE.

Results

Among 673 patients included in this analysis (UPA30, n = 229; UPA15, n = 221; PBO, n = 223), all efficacy endpoints were achieved by a greater proportion of patients receiving UPA at either dose vs PBO at week 52 (Table). More patients receiving UPA achieved the co‑primary endpoints of clinical remission (per SF/APS: UPA30, 49.3%; UPA15, 33.9%; PBO, 15.2%; per CDAI: UPA30, 51.5%; UPA15, 36.2%; PBO, 15.2%; P < .0001 for both UPA doses vs PBO) and endoscopic response (UPA30, 40.7%; UPA15, 27.3%; PBO, 7.2%; P < .0001 for both doses vs PBO) over 52 weeks. Rates of any adverse events (AEs), serious AEs, and severe AEs were numerically lower with UPA compared with PBO. The rates of most AEs of special interest were similar between UPA and PBO, with the exception of higher rates of herpes zoster, neutropenia, and creatine phosphokinase elevation in the UPA30 group. Hepatic disorders (mostly transaminase elevations) were reported more frequently with UPA than PBO. One gastrointestinal perforation was reported in each of the three treatment groups. No deaths, active tuberculosis, lymphoma, nonmelanoma skin cancer, major adjudicated cardiovascular events, or venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were reported for any treatment arm.

Conclusion

Both UPA maintenance doses were more efficacious than PBO for achieving clinical and endoscopic endpoints and had a tolerable safety profile with no new safety signals. Response and remission rates were numerically higher for patients receiving UPA30 compared with UPA15. These results are consistent with published data³ and further support the use of UPA as maintenance therapy in this patient population.

References

1. Loftus E, et al. United European Gastroenterol J. 2022;10:OP129.
2. Colombel JF, et al. Gastroenterology. 2022;162:867f.
3. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
4. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
5. Electronic Medicines Compendium. Rinvoq (upadacitinib) 30 mg prolonged-release tablets: summary of product characteristics. Updated March 16, 2023. Accessed March 27, 2023. https://www.medicines.org.uk/emc/product/12830/smpc/

Disclosure

MR has received research support from AbbVie, Janssen, and Takeda and unrestricted educational grants from AbbVie, Janssen, Pfizer, Salix, Shire, Takeda, and UCB; and has served on advisory boards and as a consultant for AbbVie, Allergan, Amgen, Celgene, Janssen, Miraca Labs, Pfizer, Seres, Takeda, and UCB.
SDL has served as a consultant for Cornerstones, Janssen, Lilly, Pfizer, and UCB; and received grant and research support from AbbVie, Arena, Celgene, Janssen, Shield Therapeutics, Takeda, Tetherex, and UCB.
RA has served as a speaker or consultant, or received research grants from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD, Novartis, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda, and Tillotts Pharma.
EB has received speaking honoraria fees from AbbVie, Ferring, Janssen, and Takeda.
CR has received consultancy and/or speaking honoraria fees from AbbVie, Ferring, Galapagos, Janssen, Pfizer, and Takeda.
AAvB has served as a consultant or speaker for AbbVie, Arena, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda, Teva, Tramedico, Vifor, and Dutch Ministry of Health (ZonMW); received research grants from Ferring, Pfizer, and Teva; and has performed as principal investigator in studies sponsored by Abivax, Arena, Celltrion, Janssen, Pfizer, Roche, and Teva.
ED, APL, JL, TF, ZG, VPR, and SIA are employees of AbbVie and may own stock and/or options.
JP has received financial support for research from AbbVie and Pfizer; received lecture fee(s) from AbbVie, Ferring, Janssen, Takeda; and received consultancy fees from AbbVie, Arena Pharmaceuticals, Athos, Boehringer Ingelheim, Celltrion, Ferring, Galapagos, Genentech, GSK, Janssen, Mirum, Morphic, Origo, Pandion, Pfizer, Protagonist, Revolo, Robarts, Roche, Takeda, Theravance, and Wassermann.
Funding
AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients who participated in the study and all study investigators for their contributions. AbbVie funded the research for this study and provided writing support for this abstract. Medical writing assistance, funded by AbbVie, was provided by Spencer Hughes, PhD, of JB Ashtin.