Introduction

Assessing the early improvement of rectal bowel wall thickness (BWT) by transperineal ultrasound (TPUS) was reported to be useful in predicting symptomatic improvement in ulcerative colitis (UC)¹. However, its predictive value for endoscopic improvement has not been demonstrated.

Aims & Methods

This is a post hoc analysis of a prospective study enrolling patients with active UC who (1) underwent induction therapy with biologics or tofacitinib, (2) underwent TPUS at baseline, week 1 and week 8. histo-endoscopic mucosal improvement (HEMI) was defined as simultaneous endoscopic improvement (Mayo endoscopic subscore ≤1), and histological improvement (Geboes score <3.1) based on colonoscopy after >14 weeks post-treatment. Improvement of rectal BWT in patients who achieved HEMI (HEMI group) was compared with that in patients who did not (non-HEMI group). For statistical analysis, a Wilcoxon signed-rank test was used. Area under the receiver operating curve (AUC) was used to determine optimal cut-off values.

Results

Of 69 patients, 11 (16%) achieved HEMI after treatment with advanced therapy (anti-TNF agents 26, vedolizumab 19, tofacitinib 14, ustekinumab 10). Patients in the HEMI group showed a reduction of rectal BWT over time in response to treatment (7.3±1.3, 6.1±1.1, 5.6±2.2 (mm) at baseline, week 1, week 8 respectively) but not in the non-HEMI group (6.4±1.5, 6.3±1.7, 5.3±2.3 (mm) at baseline, week 1, week 8 respectively). ΔRectal BWT at week 1 in the HEMI group was larger than the non-HEMI group (1.2±0.7 vs. 0.0±1.4, p=0.0043), whereas ΔRectal BWT at week 8 in the HEMI group was not significantly higher than the non-HEMI group (1.2±1.5, 0.7±2.0, p=0.30). ΔRectal BWT at week 1 predicted HEMI with high accuracy (AUC 0.79 [95% confidence interval, 0.65-0.88], p=0.02) (Table 1).

Table 1. The performance and receiver-operating characteristics of rectal bowel wall thickness at predicting the non-disease clearance at different cut-off values.

Conclusion

Monitoring the improvement of rectal wall thickening as early as week 1 is a useful strategy in predicting future biologics-induced HEMI in UC.

References

1. Sagami S, Kobayashi T, Aihara K, et al. Early improvement in bowel wall thickness on transperineal ultrasonography predicts treatment success in active ulcerative colitis. Alimentary pharmacology & therapeutics. 2022; 55 (10):1320-1329.

Disclosure

Shintaro Sagami served as a speaker for AbbVie, Takeda Pharmaceutical, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, and Zeria Pharmaceutical and as an endowed chair for AbbVie, JIMRO, Zeria Pharmaceutical, Kyorin Pharmaceutical, Mochida Pharmaceutical, and EA Pharma. Taku Kobayashi served as a speaker, a consultant, and an advisory board member for AbbVie, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceutical, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Thermo Scientific, and Zeria Pharmaceutical and received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific, and Zeria Pharmaceutical.Masaru Nakano served as a speaker/consultant at Covidien, Mochida Pharmaceutical, Takeda Pharmaceutical, Zeria Pharmaceutical, Kyorin Pharmaceutical, and Nippon Kayaku and received research funding from Mitsubishi Tanabe Pharma and the Japanese Foundation for Research and Promotion of Endoscopy. Toshifumi Hibi served as a speaker, a consultant, and an advisory board member for Aspen Japan K.K, JIMRO, AbbVie, Takeda Pharmaceutical, Zeria Pharmaceutical, Mitsubishi Tanabe Pharma, Kyorin Pharmaceutical, Ferring, Gilead Sciences, Janssen Pharmaceutical, Kissei Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly, and Nichi-Iko Pharmaceutical and received research funding from AbbVie, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Takeda Pharmaceutical, Zeria Pharmaceutical, Kyorin Pharmaceutical, and Otsuka Holdings. None of the funding received for this work was from any of the above organizations. The authors not listed have no conflicts of interest to declare.

Introduction

Several therapeutic options are now available for the treatment of moderate-to-severe ulcerative colitis (UC): pivotal trials have reported efficacy and safety of anti-TNF-α, Vedolizumab (VDZ), Ustekinumab (USTE) and Tofacitinib (TOFA) but comparative data are scanty and only one head to head trial (Varsity trial) is available. Network meta-analysis from Singh et al. demonstrated that TOFA and USTE are the best options in anti-TNF exposed patients. Real-worlds studies are discrepant most reporting similar efficacy of second-line drugs. Thus, the optimal sequence of therapeutic choices is still unclear.

Aims & Methods

Our aim was to analyze comparative efficacy of VDZ, TOFA and USTE in a homogeneous cohort of UC patients in a real life setting. We report data of a retrospective-prospective study conducted between 2020 and 2023 in our tertiary referral center. The primary outcome (PO) was clinical response (assessed by partial Mayo score). Secondary outcomes were: steroid-free remission (SFR), adverse events (AEs), time and reasons for treatment discontinuation, surgery and hospitalization rate. All outcomes were investigated at 8 weeks and at the end of follow-up (FU). At the end of FU another secondary outcome was therapy optimization. All data were analysed using the Medcalc program.

Results

73 patients (65,75% males, mean age 55 yrs) with moderate-to-severe UC were included, mostly (84%) anti-TNF experienced, treated with TOFA (27,4%), USTE (26%) or VDZ (46.6%). Average FU was 11 months. TOFA showed a significant higher clinical response rate at week 8 (80% vs 58,8% VDZ and 42,1% USTE; p = 0,016) while there were no significant differences at the end of FU. SFR rate didn’t reach the statistical significance at week 8 and at the end of FU (55% TOFA, 58,8% VDZ and 47,37% UST). 4 patients experienced AEs: 2 paresthesias and 1 mild AST/ALT elevation in the TOFA group; 1 fever of unknowkn origin (FUO) in the USTE group. Treatment discontinuation rate didn’t show significant differences. All discontinuations were for treatment failure except the patient with FUO. All the other AEs showed spontaneous resolution. None of the patients was submitted to surgery or hospitalized. Optimisation rate at the end of FU was higher in the VDZ group (50% vs 25% TOFA and 15,8% USTE ; p value (VDZ vs UST 0,009; VDZ vs TOFA 0,05).

Conclusion

TOFA was more effective at wk 8 in comparison with USTE in agreement with previous studies which have documented an increased speed of action of JaK-inhibitors. In the long run efficacy results are similar, thus not confirming superiority of TOFA and USTE as compared to VDZ observed in other studies and reported by national and European guidelines. Treatment optimization was more frequently required with VDZ. Further head-to-head trials and real-world studies are needed to investigate the comparative efficacy of second-line therapeutic agents after anti-TNF failure.

Disclosure

I

Introduction

Bowel urgency (BU) is the sudden or immediate need to have a bowel movement. Although it is a common symptom in ulcerative colitis (UC), its burden is poorly known. We aimed to assess the overall burden of UC patients with BU.

Aims & Methods

The THEFAR study is a non-interventional, cross-sectional and multicenter study carried out in France between July and December 2022 including adult patients with UC treated with biologics/targeted-synthetic drugs. Clinical and therapeutic management data were collected by gastroenterologists using a e-CRF. Quality of life, disability and work impairment (WPAI:UC) were collected using patient-self completion questionnaires. BU was defined as a UNRS (0-10 Urgency Numeric Rating Scale) >1, BU remission as a URNS ≤1 and incontinence as a Wexner score ≥5. Descriptive statistics and bivariate analyses were performed. Continuous variables were summarized with mean values and SDs using the Student’s t-test or Wilcoxon test. Categorical variables were expressed as proportions and compared using the Pearson's Chi-Squared test or Fischer's exact test.

Results

Of the 293 patients enrolled at 41 sites, the median (IQR) age was 42.0 (31.0-55.0) years with a median (IQR) disease duration of 6.0 (3.0-11.0) years. 64.2% were employed. Respectively, 45 (15,4%), 117 (39.9%) and 131 (44.7%) had proctitis, left-side colitis and pancolitis. 38.9% had active disease (partial Mayo score ≥2) and 53.6% experienced flares over the past year. Overall, 144 (49.1%) of patients were treated with TNF-inhibitors, 99 (33.8%) with vedolizumab, 35 (11.9%) with ustekinumab, and 13 (4.4%) with tofacitinib with a median treatment duration of 1.0 year (0.0 - 3.0). Of the 291 patients who answered patient-self completion questionnaires, 57.0% had BU [median (IQR) UNRS: 2 (0.0-6.0)] and 78.3% had fecal incontinence [median (IQR) Wexner score: 8.0 (5.0-11.0)] with 14.7% wearing pads at least once a month. Overall, half of patients (52.3%) had both BU and fecal incontinence. A significantly higher proportion of patients had active disease with BU (57.2%) compared to those with BU remission (15.2%) (p<0.0001). Patients with BU had twice more months flaring over the past year (2.3 vs 1.0 month, p<0.0001) and a significantly higher proportion of patients with BU (45.8% vs 14.4%, p<0.0001) received steroids over the past year. Rates of BU were similar regardless of disease location (p=0.74), UC treatment (all UC treatments p>0.05) or line of therapy (p=0.27). Median (IQR) Wexner score was almost twice higher in patients with BU [10.0 (8.0-13.0) vs 6.0 (0.0-8.0), p<0.0001]. QoL was significantly impacted in patients with BU with lower mean (SD) EQ-5D-5L utility [0.846 (0.186) vs 0.943 (0.099), p<0.0001] and Visual Analogue Scale (VAS) scores [66.2 (18.2) vs 82.1 (14.5), p<0.0001]. There was a significantly higher proportion of patients with moderate to severe disability (IBD-DISK score ≥40) in patients with BU (53.7% vs 16.9%, p<0.0001) and BU was significantly associated with the IBD-DISK (r=0.52447, p<0.0001). Mean (SD) absenteeism [11.5% (25.4) vs 3.9% (12.5), p=0.0013], overall work impairment [35.7% (29.4) vs 11.3% (18.9), p<0.0001] and activity impairment [33.0% (27.0) vs 7.9% (13.7), p<0.0001] were significantly higher in patients with BU.

Conclusion

Despite advances in UC therapies, more than one in two patients treated with biologics/targeted-synthetic drugs experience BU. Patients with BU have a high symptom burden, disability and impaired quality of life and work productivity. These findings highlight that the control of BU remains an unmet medical need in UC patients.

Disclosure

AbbVie, Ferring, Janssen, MSD, Takeda, Pfizer, Celgene, Biogen, Amgen, Boehringer Ingelheim, Lilly, Hospira et Celltrion

Introduction

Patients with immune mediated inflammatory diseases (IMIDs) on immunosuppressive therapies have attenuated vaccine responses (1-3) and are prone to severe infections. Knowledge of COVID-19 outcome following vaccine and hybrid immunity, and identification of protective anti-Spike antibody concentrations are important to further develop vaccine strategies in this vulnerable patient group.

Aims & Methods

In this prospective observational study, adult patients with IMID on immunosuppressive therapies were followed from February 15, 2021, to February 15, 2023. Throughout the study, patients and controls reported data regarding COVID-19, COVID-19 related hospital admissions were recorded from The Norwegian Patient Registry. Anti-Spike antibodies were assessed 2-4 weeks following vaccination and COVID-19. The objectives of this study were to investigate the outcomes of COVID-19 in a large cohort of IMID patients compared to healthy controls, and to identify any associations between anti-Spike antibody concentrations and disease course.

Results

Of 2250 IMID patients included in the study, a total of 1729 with a documented COVID-19 history were included in the present analyses (305 Crohn’s disease, 215 ulcerative colitis, 648 rheumatoid arthritis, 272 psoriatic arthritis, and 289 spondyloarthritis) (median age 54 years (IQR 42-64), 971 (56 %) females). Of the patients, 1080 of 1729 (62%) used anti-TNF treatment (65% monotherapy, 35% combination therapy).
1140 (66%) of patients and 236 of 350 (67%) healthy controls (HC) reported COVID-19, the majority (85%) within the Omicron era. COVID-19 reinfection was reported in in 141 (12%) patients and 32 (14%) HC (p=0.66). Compared to hybrid immunity (COVID-19 after three vaccine doses), the risk of COVID-19 was six times higher following vaccine series only (HR 5.9, (95% CI [4.45, 7.80]), p<0.001). Anti-Spike antibody concentrations <8000 BAU/ml were predictive of COVID-19 after three (HR 1.5 (95% CI [1.14, 1.90]), p=0.003) and four vaccine doses (HR 1.4 (95% CI [1.13, 1.83]), p=0.003), and in hybrid immunity (HR 2.6 (95% CI [1.32, 5.13]), p=0.006). In the entire cohort, the median anti-Spike antibody concentration after the 2^nd vaccine dose was 2823 BAU/ml (IQR 999-6199), after the 3^rd dose 6529 BAU/ml (IQR 2325-10140), after the 4^th dose 7624 BAU/ml (3809-12751) and following hybrid immunity 23506 BAU/ml (11423, 37007). Hospitalisation due to COVID-19 (severe disease) occurred in 22 (2%) patients, 9 (41%) before any vaccination, and none of HC. Four patients were admitted to intensive care. Prior to hospitalisation, the median anti-Spike antibody concentration was 444 BAU/ml (IQR 31-1634). Patients with severe disease were older than non-hospitalised (median age 61 years (IQR 48-74) vs. 54 (42-64), p=0.04) and had a higher frequency of comorbidities (19/22 (86%) vs. 474/1118 (42%), p=0.02). No COVID-19 related deaths occurred.
Prolonged COVID-19 (symptoms >14 days) were reported by 201 (18%) patients compared to 29 (12%) HC (p=0.09). The risk of prolonged disease was higher in the vaccine group compared to the hybrid group (HR 8.5 (95 % CI [3.84, 18.90]), p<0.001).

Conclusion

IMID patients and healthy controls had a comparable occurrence of COVID-19, prolonged disease and reinfection. However, severe disease developed only in the patient group. Hybrid immunity protects against COVID-19 and prolonged disease. A high anti-Spike antibody concentration protects against COVID-19, supporting the role of repeated vaccination in IMID patients on immune-suppressive therapy.

References

1. Jorgensen KK, Hoivik ML, Chopra A, Benth JS, Ricanek P, Moum PB, et al. Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scand J Gastroenterol. 2023:1-9.
2. Bjorlykke KH, Orbo HS, Tveter AT, Jyssum I, Sexton J, Tran TT, et al. Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. Lancet Rheumatol. 2023;5(1):e36-e46.
3. Syversen SW, Jyssum I, Tveter AT, Tran TT, Sexton J, Provan SA, et al. Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis Rheumatol. 2022;74(8):1321-32.

Disclosure

Have received speakers bureaus from Bristol-Myers Squibb and Roche

Introduction

Double-headed capsules enable the non-invasive one-step endoscopic evaluation of both the small bowel and colon (pan-intestinal capsule endoscopy, PCE).

Aims & Methods

We aim to evaluate the diagnostic accuracy and safety of PCE vs. the current standard of care (conventional colonoscopy) as the first-line examination in patients with iron deficiency anaemia (IDA) and/or overt bleeding after a non-diagnostic upper endoscopy (suspected mid or lower gastrointestinal bleeding, MLGIB).
We conducted a prospective, single-centre, single-blinded cohort study including consecutive patients with suspected MLGIB. All patients were submitted to PCE, followed by same-day colonoscopy under deep sedation. The physicians performing PCE and conventional colonoscopies were independent and blinded to each other’s observations. The diagnostic yield for potentially haemorrhagic lesions (PHL) was compared for efficacy analysis, and adverse events were assessed for both examinations. The gold standard diagnosis was defined by consensus panel. This trial has been registered in ClinicalTrials.gov (ID NCT04782986).

Results

We included 100 consecutive patients with suspected MLGIB, mean age 66.5 (18-92) years, 65% female gender, presenting with IDA (81%) or overt bleeding (19%). Mean haemoglobin level was 8.4 (4.1-12.8) g/dL and 40% were inpatients. For PCE, the PillCam Crohn’s® capsule was used in 88 patients, and PillCam COLON® 2 in the remaining. Patients with overt bleeding performed PCE within 2 weeks in 70% of cases, 15% in the first 72h after the bleeding episode. PCE was complete in 76% of cases, vs. colonoscopy 95% (p<0.01). The quality of bowel preparation was adequate in 72% of PCE vs. 85% of colonoscopies (p=0.012). Overall, PHL were diagnosed, based on the combination of PCE + colonoscopy, in 46% of patients, corresponding to small bowel and/or colon angioectasias in more than two-thirds (69.6%) of cases. PHL were detected by both examinations in 13/46 (28.3%), only by colonoscopy in 3/46 (6.5%), and only by PCE in 30/46 (65.2%) of cases (p<0.01). Overall, colonoscopy detected PHL in 23% of the entire cohort, which means 50% (23/46) of all patients with PHL according to the consensus panel, while for PCE the overall diagnostic yield was 44%, meaning 95.7% (44/46) of all PHL (p<0.01). Considering the gold standard diagnosis for PHL, colonoscopy had a sensitivity of 23/46=50%, specificity 54/54=100%, positive predictive value (PPV) 23/23=100% and negative predictive value (NPV) 54/77=70,1%, while for PCE the sensitivity was 44/46=95.7%, specificity 54/54=100%, PPV 44/44=100% and NPV 54/56=96.4%. Thirty-one percent of patients had PHL accessible to ileocolonoscopy; in those cases, the PCE was able to make the diagnosis in 29/31 (93.5%) vs. conventional colonoscopy in 23/31 (74.2%) of cases, p<0.01. Regarding safety, no significant adverse events occurred with PCE, vs. 2% (cardiopulmonary) with conventional colonoscopy.

Conclusion

PCE is safe and more effective than conventional colonoscopy in identifying PHL both in the small bowel and the colon, and could be considered as a first-line examination in patients with IDA or overt bleeding after a non-diagnostic upper endoscopy. In more than half of patients with suspected MLGIB, PCE does not detect any PHL either in the small bowel or the colon, dismissing any further invasive endoscopic investigations.

Disclosure

Medtronic provided financial support to the acquisition of some of the capsules which were used in the trial

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.