Introduction

Phase III trials have demonstrated the efficacy of risankizumab (RZB), this being the first humanised monoclonal IgG1 antibody which targets the interleukin 23 p19 subunit, in moderate-to-severe Crohn's disease (CD). However, real-world data in induction with this drug is scarce. The aim of the study was to assess the real-world short-term effectiveness and safety of RZB in multi-refractory patients with CD.

Aims & Methods

Adult CD patients that had received induction doses with RZB in the ENEIDA registry—a large prospectively maintained Spanish database promoted by the Spanish Working Group in Crohn’s and Colitis (GETECCU)— were included. Clinical and demographical data including number of previous biologics and advanced therapies were included. The primary endpoint was steroid-free clinical remission evaluated at any point between weeks 8 and 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included steroid free clinical remission at the end of follow-up, clinical, biochemical improvement (C-reactive protein (CRP) and/or faecal calprotectine (FC)), need for CD-related surgery and adverse events related with the drug. The data are presented as median (range), and frequencies and percentages. Statistical analysis was performed using the Chi-square or Fisher's test, and the Student-t test or U-Mann-Whitney test as appropriate.

Results

417 CD patients (52% male) were included: median age was 50 (18-84) years, median disease duration 14 years, 27% were smokers. Regarding Montreal classification, 49% were L1, 10% L2, and 38% L3. Most of the patients presented inflammatory pattern (47%), 32% presented structuring, 21% penetrating behavior and perianal disease was present in 24%. 48% had abdominal CD surgery and 41% presented extraintestinal manifestations. Only 8% received concomitant immunossupressives with RZB. Regarding previous exposure to biologics or JAK inhibitors, only 3% were naïve, 49% had been exposed to 1-2 advanced therapies and 48% to 3 or more biologics or JAKs. After induction 58% of the patients achieved steroid-free clinical remission and at the end of the follow-up steroid-free clinical remission was observed in 62% of the patients. Median FC decreased from week 530 μg/g (week 0) to 333 μg/g after induction (p <0.001). Regarding CRP, this decreased from median 7 mg/L at week 0 to 4.7 mg/L after induction (p = 0.002). 15 patients (3.5%) underwent intestinal resection. 23 patients (5.5%) presented adverse events including 6 infections.

Conclusion

This is the largest cohort study of real-world data with RZB, and it includes highly refractory patients with CD and multiple prior drug failures. RZB induction provided a steroid-free clinical remission in nearly 60% of patients and a significative improvement in biomarkers. Safety was consistent with the known profile of RZB in previous trials.

Disclosure

MBA has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, GALAPAGOS, Pfizer, Sandoz, Biogen, Fresenius, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Adacyte and TillotsPharma.

Introduction

The BIOSTOP Trial is a prospective, multicenter, randomized, controlled, open-label study conducted in Norway to evaluate the two-year outcomes of tumor necrosis factor-alpha (anti-TNF) antibody withdrawal in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission. Prior non-randomized studies have suggested that approximately half of such patients maintain remission after anti-TNF discontinuation and that reintroduction of anti-TNF therapy is generally effective and safe in the event of relapse.

Aims & Methods

A total of 174 UC patients in confirmed clinical and endoscopic remission were enrolled across 19 gastroenterology centers between June 2017 and December 2020 and randomized 1:1 to either continue or discontinue anti-TNF therapy. Eligibility criteria included at least 12 months of first-line anti-TNF maintenance treatment, clinical remission, fecal calprotectin <200 µg/g, and endoscopic remission (Mayo endoscopic score 0 or 1). Two-year follow-up data were available for 172 patients (86 in each group). In 156 of the patients endoscopies were available for central reading (77 in the withdrawal group and 79 in the maintenance group). The primary endpoint was sustained endoscopic remission at two years.

Results

At two years, central reading of follow-up colonoscopies confirmed endoscopic remission in 64 of 77 patients (83%, 95% CI 71.8 – 93.1) in the anti-TNF withdrawal group, compared to 77 of 79 patients (96 %, 95 % CI 92.1 – 100.8) in the anti-TNF maintenance group. The non-inferiority primary endpoint of the study was thus not met. During the study period, 48% of patients in the withdrawal group and 88% in the maintenance group remained in sustained clinical and endoscopic remission without relapse. Among the 45 patients in the withdrawal group who experienced endoscopic confirmed relapse, 28 (62%) resumed anti-TNF therapy, with 26 achieving both clinical and endoscopic remission. Additionally, 10 of 13 patients with mild relapses achieved endoscopic remission with optimized non-biologic therapy. There were no difference in serious adverse events between the groups.

Conclusion

After two years, 83% of patients in the anti-TNF withdrawal group and 96% in the maintenance group were in clinical and endoscopic remission, including those who experienced flares and achieved new remission after reintroduction of anti-TNF or optimized non-biologic therapy. Nearly half of the patients maintained remission without anti-TNF, and the majority of relapses were effectively managed. These findings suggest that anti-TNF withdrawal is a safe option for selected UC patients in confirmed remission, provided they are monitored closely.
Trial Registration: ClinicalTrials.gov Identifier: NCT03011268; EudraCT Number: 2016-001409-18. Trial completion date: 31 January 2025.

Disclosure

No disclosures

Introduction

Inhibition of interleukin (IL)-23 has been demonstrated as a safe and effective mechanism of action for treating various chronic inflammatory diseases, including Crohn's disease (CD). The phase 3b SEQUENCE study directly compared the efficacy and safety of risankizumab (RZB), a selective IL-23 p19 subunit inhibitor, and ustekinumab (UST), an IL-12/IL-23 p40 subunit inhibitor, in patients (pts) with moderate to severe CD.

Aims & Methods

SEQUENCE, an open-label, multicenter, randomized, efficacy assessment-blinded study, enrolled pts who previously failed ≥1 anti-TNF therapies and had a CD Activity Index score of 220-450, Simple Endoscopic Score for CD ≥6 for ileocolonic or colonic disease (≥4 for isolated ileal disease) excluding the presence of narrowing component, plus an average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2. In Part 1 of the trial, described herein, pts were randomized 1:1 to receive RZB (600 mg IV induction dosing at baseline [BL], weeks [wks] 4 and 8, followed by 360 mg SC maintenance dosing every 8 wks [Q8w] starting at wk12) or UST (a single weight-based IV induction dose, followed by 90 mg SC maintenance dosing Q8w starting at wk8) over a period of 48 wks.¹ Randomization was stratified by number of anti-TNF therapies failed (1, >1) and steroid use at BL (Y, N). A mandatory steroid taper started at wk2. Two primary endpoints were clinical remission at wk24 (non-inferiority of RZB vs UST in 50% of planned subjects) and endoscopic remission at wk48 (superiority of RZB vs UST). Ranked secondary endpoints included clinical remission at wk48, endoscopic response at wks 48 and 24, steroid-free (SF) endoscopic remission at wk48, and SF clinical remission at wk48 (all tested for superiority of RZB vs UST). Safety was assessed throughout the trial.

Results

Variable	RZB N=255 n/N (%)	UST N=265 n/N (%)	Treatment Difference RZB – UST % [95% CI]
Primarya 1. Clinical remission at wk 24 (ITT-1Hb) 2. Endoscopic remission at wk 48 (ITT-1d) Ranked Secondarya,d 1. Clinical remission at wk 48 2. Endoscopic response at wk 48 3. Endoscopic response at wk 24 4. Steroid-free endoscopic remission at wk 48 5. Steroid-free clinical remission at wk 48	75/128 (58.6%) 81/255 (31.8%) 155/255 (60.8%) 115/255 (45.1%) 115/255 (45.2%) 80/255 (31.4%) 155/255 (60.8%)	54/137 (39.5%) 43/265 (16.2%) 108/265 (40.8%) 58/265 (21.9%) 70/265 (26.4%) 41/265 (15.5%) 107/265 (40.4%)	Non-inferiorityc met; 18.4 [6.6, 30.3] 15.6 [8.4, 22.9], P<0.0001 19.7 [11.3, 28.1], P<0.0001 23.3 [15.4, 31.2], P<0.0001 18.9 [10.9, 26.9], P<0.0001 15.9 [8.8, 23.1], P<0.0001 20.1 [11.7, 28.4], P<0.0001
Treatment Emergent Adverse Events (AEs)e	RZB N=262 PYs = 257.6 Events (E/100PYs)f	UST N=265 PYs = 269.9 Events (E/100PYs)f	Treatment Difference RZB – UST % [95% CI]
All TEAEs Investigator-defined drug-related AEg,h Severe AE Serious AE AEs leading to study drug discontinuation Death Adverse Events of Special Interest Adjudicated MACE/Extended MACEi Serious infections Active tuberculosis Opportunistic infections excluding tuberculosis and herpes zosterj Herpes zoster Malignant tumoursk Non-melanoma skin cancer (NMSC) Malignancies excluding NMSC Hypersensitivity Serious hypersensitivity Adjudicated anaphylactic reaction Hepatic events Injection site reactions	879 (341.2) 167 (64.8) 60 (23.3) 36 (14.0) 10 (3.9) 0 0 10 (3.9) 0 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 0 37 (14.4) 0 0 26 (10.1) 5 (1.9)	763 (282.7) 111 (41.1) 82 (30.4) 64 (23.7) 14 (5.2) 0 1 (0.4) 14 (5.2) 0 0 1 (0.4) 1 (0.4) 0 1 (0.4) 32 (11.9) 0 0 23 (8.5)i 8 (3.0)	58.5 (28.3, 88.7) 23.7 (11.2, 36.2) -7.1 (-15.9, 1.7) -9.7 (-17.1, -2.4) -1.3 (-4.9, 2.3) 0 -0.4 (-1.1, 0.4) -1.3 (-4.9, 2.3) 0 0.4 (-0.4, 1.1) 0.0 (-1.0, 1.1) 0.0 (-1.0, 1.1) 0.4 (-0.4, 1.1) -0.4 (-1.1, 0.4) 2.5 (-3.7, 8.7) 0 0 1.6 (-3.6, 6.8) -1.0 (-3.7, 1.6)
AE – adverse event; BL - baseline; CD – Crohn’s disease; CDAI – CD activity index; ITT – intention to treat; RZB - risankizumab; PY, patient years; SES-CD, simple endoscopic score for CD; TEAE – treatment emergent AE; UST – ustekinumab; wk, week Clinical remission – CDAI < 150 Endoscopic remission - SES-CD ≤ 4 and at least a 2-point reduction versus BL and no sub score greater than 1 in any individual variable, as scored by a central reviewer blinded to treatment allocation Endoscopic response - decrease in SES-CD > 50% from BL (or for pts with isolated ileal disease and a BL SES-CD of 4, at least a 2-point reduction from BL), as scored by central reviewer Steroid-free endoscopic remission - endoscopic remission and not receiving steroids at the corresponding visit Steroid-free clinical remission - clinical remission and not receiving steroids at the corresponding visit *SEQUENCE Part 1 compared the efficacy and safety of RZB versus UST over 48 wks, while Part 2 is an ongoing open-label long-term extension to evaluate the long-term safety of RZB in pts who received RZB in Part 1 and completed wk48 visit. aCategorical variables were analyzed using Cochran-Mantel-Haenszel (CMH) test. For both the primary and secondary endpoints, the non-responder imputation while incorporating multiple imputation to handle missing data (due to COVID-19 or geopolitical conflict) was used. Primary and secondary endpoints were tested sequentially in the order specified using the CMH risk difference estimate test stratified by the number of failed anti-TNF therapies (1, > 1) and steroid use at baseline (yes, no). bITT1H population is a subset of ITT-1 population and includes approximately 50% of ITT1 subjects who have opportunity to reach wk24 by the time of the primary analysis of CDAI clinical remission at wk24; non-inferiority of RZB vs. UST cNon-inferiority test: If the lower limit of 95% confidence interval based on the CMH estimation for the risk difference between RZB and UST groups (RZB – UST) was greater than the negative of 10% noninferiority margin, then noninferiority was demonstrated for clinical remission at wk24. If non-inferiority was demonstrated for clinical remission (CDAI) at Week 24, the superiority for the endoscopic remission at Week 48 was subsequentially tested at two-sided significance level of 0.05 using the CMH test. dIntent-to-treat-1 (ITT-1) population included all randomized subjects who were randomized to RZB with the selected RZB dose (RZB 600 mg IV followed by RZB 360 mg SC) or UST and who received at least 1 dose of study drug during Part 1 of the study; superiority of RZB vs. UST eTEAEs are events that begin either on or after the first dose of UST or RZB in Part 1 and until the first dose of study drug (RZB) in Part 2 if the pt is enrolled into the Part 2 or within 140 days after the last dose administration of the study drugs (UST or RZB) in Part 1 if the pt does not participate in Part 2. Only safety data obtained before 12JUL2023 or Week 52 dosing date (the first dose date of Part 2), whichever occurred earlier, are reported here. fSA1 population includes all pts who received at least 1 dose of study drug during Part 1 of the study. gAs assessed by investigator hRZB related: 3 patients with SAEs related to RZB (anal fistula, anal abscess, campylobacter, cystitis, localized infection, genital fistula); 8 patients with SAEs related to UST (abdominal pain, anal fistula, CD, ileal stenosis, vomiting) iMACE: Major Adverse Cardiovascular Events, defined as cardiovascular death or death due to stroke, non-fatal myocardial infarction, and non-fatal stroke; extended MACE defined as MACE with hospitalization for unstable angina and coronary revascularization procedures jOpportunistic infection: RZB, oesophageal candidiasis kMalignant tumor: RZB, squamous cell carcinoma of skin; UST, anal squamous cell carcinoma iOne case of potential Hy’s Law in the UST treatment group

In total, 520 pts were randomized and assessed for efficacy: RZB (N=255) and UST (N=265). The proportion of pts who completed the study was numerically higher with RZB (89.4%) vs UST (74.0%). The two primary endpoints of the study were met. At wk24, in half of the patients enrolled, clinical remission rates were 58.6% (75/128) for RZB and 39.5% (54/137) for UST (Δ18.4 [6.6-30.3], non-inferiority met with the pre-defined margin of 10%) (Table). At wk48, endoscopic remission rates were 31.8% (81/255) for RZB and 16.2% (43/265) for UST (Δ15.6% [8.4-22.9], P<0.0001 for superiority). RZB was superior to UST for all secondary endpoints (all P<0.0001). Exposure adjusted adverse event (AE) rates (Events [E/100PYs]) were comparable between RZB (879 [341.2]) and UST (763 [282.7]). Rates of serious AEs and AEs leading to study drug discontinuation were numerically higher with UST than RZB (Table). Rates of serious infections and hepatic events were similar between treatment groups, with no serious hepatic events with RZB. Two cases of malignancy were reported (one in each treatment arm). There was one event of adjudicated MACE with UST. There were no deaths.

Conclusion

In pts with moderate to severe CD who failed anti-TNF therapy, RZB demonstrated non-inferiority to UST in achieving wk24 clinical remission, superiority in achieving wk48 endoscopic remission, and superiority for achieving all secondary endpoints. The safety profiles of RZB and UST were consistent with previously published results.

References

1. Stelara Label [Internet]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125261s161lbl.pdf

Disclosure

Laurent Peyrin-Biroulet: Fees: Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index, Sandoz, Celgene, Biogen, SamsungBioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSEImmunotherapeutics, Enthera, Theravance, Pandion, Gossamer, Viatris, ThermoFisher, ONOPharma, Mopac, Cytoki, Morphic, Prometheus, Applied MolecularTransport; J. Casey Chapman: Consultant: AbbVie, Medtronic; Advisory Board: AbbVie, Pfizer, Takeda; Speaker: AbbVie, BMS, Janssen, Pfizer, Takeda; Jean-Frederic Colombel: Grants: AbbVie, Janssen, Takeda, BMS; Speaking fees: AbbVie, Takeda; Consultant: AbbVie, Amgen, AnaptysBio, Allergan, Arena, BI, BMS, Celgene, Celltrion, Lilly, Ferring, Galmed, GSK, Genentech (Roche), Janssen, Kaleido, Immunic, IterativeScopes, Merck, Landos, Microba Life Science, Novartis, Otsuka, Pfizer, ProtagonistTherapeutics, Sanofi, Takeda, TiGenix, Vifor; Stock options: IntestinalBiotechDevelopment; Flavio Caprioli: Consultant: AbbVie, MSD, Takeda, Janssen, Roche, Celgene, BMS, Galapagos, Gllead, Pfizer, Mundipharma, Galapagos, Biogen; Speaker: AbbVie, Ferring, Takeda, AllergyTherapeutics, Janssen, Pfizer, Biogen; Research grants: Giuliani, Sofar, MSD, Takeda, AbbVie; Geert D’Haens: Advisor: AbbVie, Ablynx, ActiveBiotechAB, AgomabTherapeutics, Alimentiv, Allergan, Alphabiomics, Amakem, Amgen, AMPharma, AppliedMolecularTherapeutics, Arena, AstraZeneca, Biogen, BMS, BI, Celltrion, DSMPharma; Echo, Engene, Exeliom, Ferring, Dr Falk, Galapagos, Genentech/Roche, Gilead, GSK, Gossamerbio, Immunic, J&J, Kintai, Lilly, Lument, Lycera, Medtronic, MSD, MitsubishiTanabe, NovoNordisk, Otsuka, Pfizer, Photopill, ProciseDx, Prodigest, Progenity, Prometheus/Nestlé, Protagonist, RedHill, SamsungBioepis, Sandoz, Seres, Setpoint, Shire, Takeda, Teva, Tillotts, Topivert, Versant, Vifor. Marc Ferrante: Grants: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda, Viatris; Consultant: AbbVie, Agomab, BI, Celgene, Celltrion, Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, SamsungBioepis, Sandoz, Takeda, ThermoFisher; Speaker: AbbVie, Amgen, Biogen, BI, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion, Viatris; Stefan Schreiber: Consultant: AbbVie, Amgen, Arena, BMS, BI, Celltrion, Dr Falk, Ferring, Fresenius, Galapagos, Genentech, Gilead, GSK, IMAB-Biopharma, Janssen, Lilly, Merck, Novartis/Sandoz, Pfizer, Protagonist, Takeda, Theravance. Raja Atreya: Speaker, consultant, or grants: AbbVie, Amgen, Arena, Biogen, BI, BMS, Cellgene, Celltrion, DrFalk, Galapagos, Gilead, InDex, Janssen-Cilag, Lilly, MSD, Novartis, Pandion, Pfizer, Roche, SamsungBioepis, Takeda, Viatris; Silvio Danese: Consultant: AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, AthosTherapeutics, Biogen, BI, Celgene, Celltrion, Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, J&J, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; Lecture fees: Abbvie, Amgen, Dr Falk, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda. James O. Lindsay: Consultant/advisory board: AbbVie, AtlanticHealthcare, BMS, Celgene, Celltrion, Lilly, Ferring, Galapagos, Gilead, GSK, Janssen, MSD, Napp, Pfizer, Shire, Takeda, Vifor; Speaker fees/sponsorship: AbbVie, Ferring, Janssen, MSD, Napp, Norgine, Pfizer, Shire, Tillotts, Takeda; Grants: AbbVie, Gilead, Pfizer, Shire, Takeda; Peter Bossuyt: Grants: AbbVie, Amgen, Janssen, Mundipharma, Mylan, Pfizer; Speaker: AbbVie, Celltrion, Janssen, Pfizer, Takeda; Advisory Board: AbbVie, Arena, BMS, Hospira, Janssen, Lilly, Merck, Mundipharma, PentaxMedical, Pfizer, PSI CRO, Roche, Sandoz, Takeda; Britta Siegmund: Consultant: AbbVie, Arena, BI, BMS, Celgene, Falk, Galapagos, Janssen, Lilly, Pfizer, Prometheus, Takeda; Speaker’s fees: AbbVie, CEDServiceGmbH, Falk, Ferring, Janssen, Novartis, Pfizer, Takeda; Peter Irving: Grants/ Fees: Janssen, MSD,Takeda; Personal fees: AbbVie, Arena, Dr. Falk, Lilly, Ferring, Genentech, Hospira, Pfizer, Pharmacosmos, SamsungBioepis, Sandoz, Shire, Tillotts, TopiVert, VHsquared, Vifor, WarnerChilcott. Remo Panaccione: Consultant: AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, BMS, BI, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Sandoz, Satisfai, Schering-Plough, Shire, Sublimity, Theravance, UCB, Takeda; Speaker: AbbVie, Arena, Celgene, Ferring, Gilead, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; Grants: AbbVie, Ferring, Janssen, Pfizer, Takeda; Advisory board: AbbVie, Amgen, Arena, BMS, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Sandoz, Shire, Sublimity, Takeda, Theravance. Marla Dubinsky: Consultant: AbbVie, Arena, BMS, Celgene, Lilly, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda; Founder/shareholder Trellus Health.
Ezequiel Neimark, Kori Wallace, Toni Anschutz, Kristina Kligys, W Rachel Duan, Valerie Pivorunas, Xiu Huang, Sofie Berg, Lei Shu: AbbVie full-time employees; may own AbbVie stock or options.

Introduction

Neoplasia detection in inflammatory bowel disease (IBD) poses a clinical challenge. We have previously reported the efficacy of a novel computer aided detection (CADe) algorithm for use in IBD (CADe-IBD) in images and videos. CADe-IBD is designed for use in high-definition white light endoscopy which may reduce operator variability which comes with chromoendoscopy. The added value of CADe-IBD is yet to be explored which this study aims to address.

Aims & Methods

Based on pilot data this study was powered as a superiority test, with 90% power for increased sensitivity of non-expert endoscopists with CADe-IBD compared to without CADe-IBD. 10 experienced and 11 less experienced endoscopists were asked to review short video clips of high definition white-light IBD endoscopy on a bespoke computer software designed by NEC Japan. The videos were watched once without CADe-IBD and then again with CADe-IBD when the videos were randomly redistributed to reduce recall bias. After each video the endoscopist was asked to select ‘polyp’, ‘no polyp’ or ‘uncertain’. If the endoscopist selected ‘polyp’ for a video they were asked to annotate the suspected abnormality.

Results

The study included 285 videos from IBD colon. 131 videos had lesions which showed a diverse range of size, morphology, histology and background mucosal inflammation. Videos were from all 3 major endoscopy processors (Pentax, Olympus and Fuji).
The standalone CADe-IBD sensitivity and specificity were 94.7% and 70.8% respectively. In comparison, experienced endoscopist sensitivity and specificity were 90.5% and 80.2% and less experienced endoscopists sensitivity and specificity of 73.7% and 82.1%. CADe-IBD sensitivity was significantly better than both experts and non-exerts (p<0.05).
With the addition of CADe-IBD, less experienced endoscopists sensitivity increased significantly to 89.2% (p <0.01) and specificity remained similar at 81.0%. Experienced endoscopist sensitivity also improved with CADe-IBD to 93.4% which was again statistically significant (p<0.05).
Sub-analysis was performed based on neoplastic or non-neoplastic histology, polypoid (Paris Is, Isp, Ip) and non-polypoid (Paris IIa/IIb/IIc) morphology and Mayo endoscopic sub-score for mucosal inflammation (Table 1).

Table 1.	CADe-IBD sensitivity	Less experienced endoscopist sensitivity	Less experienced + CADe-IBD sensitivity	Experienced endoscopist sensitivity	Experienced + CADe-IBD sensitivity
Overall (n=131)	94.7%	73.7%%	89.2%	90.5%	93.4%
Histology Neoplastic (n=62) Non-neoplastic (n=69)	96.8% 92.8%	72.6% 74.7%	90.2% 88.4%	92.1% 89.0%	95.0% 92.0%
Morphology Polypoid (n=29) Non-polypoid (n=102)	100% 93.1%	93.7% 68.0%	98.1% 86.7%	99.3% 87.9%	99.7% 91.7%
Mayo score 0 (n=105) 1 (n=21) 2 (n=5)	95.2% 90.5% 100%	74.1% 68.4% 87.3%	90.9% 80.1% 92.7%	90.7% 89.5% 90.0%	93.7% 92.9% 90.0%

Conclusion

CADe-IBD has a standalone performance which is superior to both less experienced and experienced endoscopists. The addition of CADe-IBD significantly improved lesion detection regardless of experience. This superior performance was observed in neoplastic lesions, non-polypoid lesions and in the presence of mild background mucosal inflammation which is of high clinical importance. This calls for a head to head comparison of CADe-IBD with conventional surveillance techniques.

References

Abdelrahim M, Siggens K, Iwadate Y, et al New AI model for neoplasia detection and characterisation in inflammatory bowel disease Gut 2024;73:725-728.

Disclosure

Professor Bhandari has received research grants or is the advisory board for Fujifilm, Boston, Olympus, Pentax, 3-D matrix, NEC (Japan) and Medtronic

Introduction

Response to hepatitis B vaccine (HBV) is variable in inflammatory bowel disease (IBD) patients with seroconversion rates of 34-89%. Strategies suggested to improve the seroconversion rates are double dose, accelerated schedule, or addition of booster dose with variable results. This study compared the standard (20 µg) dose and double (40 µg) dose of HBV vaccination in IBD patients.

Aims & Methods

Patients of IBD were randomized to 1:1 to receive standard or double dose of HBV at 0, 1 and 6 months. Anti-HBs titers were assessed at 1 month after the third dose. Response was defined as an adequate immune response (AIR, anti-HBs titer >10 mIU/mL) and effective immune response (EIR, anti-HBs titer >100 mIU/mL). Total mayo score and Crohn’s disease activity index (CDAI) was used to identify the active disease. IBD medications with immunosuppressive effects were categorized as immunomodulators, corticosteroids, tofacitinib and biologic group. Multivariable logistic regression analysis was done to identify the predictors of AIR and EIR.

Results

Eighty-eight patients of IBD were randomized to receive standard (45, 51.1%) or double (43, 48.9%) dose of HBV. 79 of 88 patients had ulcerative colitis (UC) and 9 had Crohn’s disease (CD). 49 (55.7%) patients had active disease while 39 (44.3%) were in remission. At the end of the study, total 63 (71.61%) patients achieved AIR and 51 (60%) achieved EIR. AIR (88.4 % vs. 55.6 %, p 0.001) and EIR (69.8% vs. 46.7%, p = 0.028) rates were significantly higher with double dose compared to standard dose of HBV. Patients with active IBD had higher AIR (87.5% vs. 44%, p = 0.001) and EIR (70.8% vs. 32%, p = 0.007) rates with double dose of HBV. Patients with IBD in remission also had higher AIR (89.5% vs. 70%) and EIR (78.4% vs. 65%) rates with double dose of HBV, though statistically non-significant.
Multivariable analysis identified the use of double dose of HBV {odds ratio (OR) 10.865, 95% confidence interval (CI): 2.418-48.817} and biologic (OR 0.022, 95% CI: 0.001-0.421) as predictors to achieve AIR. Similarly, double dose of HBV (OR 3.0, 95% CI: 1.087-8.280) and use of biologic (OR 0.074, 95% CI: 0.006-0.931) also predicted the EIR.

Conclusion

Double dose of HBV vaccine demonstrated a superiority over standard dose of vaccine for achieving both AIR and EIR. Use of biologic impaired the response. Double dose of HBV should be used in IBD patients to improve the seroconversion rates.

Disclosure

No conflict of Interest