Introduction

Subcutaneous (SC) Infliximab (IFX) is non-inferior to intravenous (IV) IFX, for maintenance of remission in inflammatory bowel disease (IBD) (1). There are limited data on factors affecting the decisions of patients who choose SC administration of biologics (2, 3). Our centre offered suitable patients SC IFX from November 2022.

Aims & Methods

(1) Determine disease-related, economic, social and personal factors that affect the decision of a patient with IBD to transition from IV to SC administration of IFX.
(2) Assess effects of SC administration on pharmacokinetics and disease control. Participants completed a questionnaire on their IBD history, personal and financial circumstances, and reasons for electing or declining to transition. Clinical and biochemical data were retrieved from the electronic patient record (EPR). A bivariable logistic regression model was used to determine factors associated with electing to transition.

Results

144 patients were offered the opportunity to transition during the study period. 80 (55.5%) agreed to transition, 64 (44.5%) declined. 101 patients (70.1%) agreed to participate in the study. 59.4% were male, 67.3% had Crohn’s disease. Age ranged was 18-82 (median 41) years. Infusion frequency was every 4 (9.8%), 6 (22.8%), 7 (2.0%), or 8 weeks (65.4%). 76% were employed/self-employed, 41.6% had a medical card and 44.6% had private health insurance. Median (IQR) travel time was 90 mins (40, 130). 48 patients (47.5%) reported that they missed school/work for their infusions. At baseline, median (IQR) laboratory results were CRP 1.2mg/L (0.6, 2.7), IFX trough 7.4mg/mL (4.9, 11.8), faecal calprotectin 39 mg/g (10, 98), IBD-Control 14 (13, 16). 8 weeks after first SC dose, median (IQR) results (n=36) were CRP 1.1mg/L (0.8, 2.0) IFX trough 17.8mg/mL (12.5, 21.4), IBD-Control 16 (14, 16). The strongest reasons to transition (% agree/ strongly agree on five-point Likert) were, “I want to transition because it will…”
(1) reduce my travel time (94.5%),
(2) fit my work/life balance better (87.3%) and
(3) reduce my time away from work/school (74.5%). The strongest reasons against transition were,
(1)I would miss having my bloods checked regularly (84.8%),
(2) I feel safer attending the infusion unit (80.4%),
(3) I would not be able to voice concerns about my treatment as easily (80.4%) and
(4) I would miss regular contact with a healthcare professional (69.6%). Table 1 shows results of binary logistic regression used to determine factors associated with the likelihood of electing to transition.

Conclusion

SC IFX is safe, effective and well-tolerated by those who choose to transition. It is attractive to many patients, because attending for IV infusions can interrupt their employment, education and family life, but cost is a significant barrier for some patients. IBD teams must be adequately resourced to assure patients who transition that they will continue to have ready access to high-quality medical care and disease monitoring. Discrepancies in healthcare markets may provide a perverse incentive to continue receiving IV biologic, for those who would prefer SC.

References

1. Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology. 2021;160(7):2340-53.
2. Remy C, Caron B, Gouynou C, Haghnejad V, Jeanbert E, Netter P, et al. Inflammatory Bowel Disease Patients’ Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience. Journal of Clinical Medicine. 2022;11(24):7296.
3. Ventress E, Young D, Rahmany S, Harris C, Bettey M, Smith T, et al. Transitioning from Intravenous to Subcutaneous Vedolizumab in Patients with Inflammatory Bowel Disease [TRAVELESS]. Journal of Crohn's and Colitis. 2022;16(6):911-21.

Introduction

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4β7) integrin, suppresses immune cell migration by blocking the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule 1, and is used to treat patients with UC with moderate-to-severe activity. Reports about histological features that predict vedolizumab efficacy are scarce.

Aims & Methods

We evaluated the infiltration of inflammatory cells in the colonic mucosa prior to the induction of vedolizumab and examined the association between histological features and vedolizumab efficacy.
This was a multicenter, retrospective study. Patients with UC who were treated with vedolizumab between November 2018 and April 2021 were enrolled in this study. All eligible patients had moderate-to-severe disease activity at the time of the initial treatment with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 per unit area of the lamina propria were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified.

Results

A total of 42 patients were included in this study. 17 (40.5%) patients achieved clinical remission at week 22. Significantly more CD4+ cells were found in the colonic mucosal tissues of patients with remission than in those without remission (odds ratio [OR]=1.44, P=0.014). In contrast, the CD68-positive area and the CD45-positive were not significantly different between the two groups. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR=0.11, P=0.008 and OR=0.50, P=0.009, respectively).

Conclusion

A high CD4+ infiltration in the colonic mucosa was associated with remission after vedolizumab treatment. Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.

Introduction

Mirikizumab, a monoclonal antibody targeting the p19 subunit of IL-23, was approved in Germany in May 2024 for the treatment of moderately to severely active ulcerative colitis (UC), following favorable results in clinical trials (1,2). We aimed to evaluate the effectiveness and safety of mirikizumab (MIRI) in a real-world setting, focusing on a population of patients with prior exposure to three or more advanced therapies.

Aims & Methods

​​​​​In October 2023, we initiated a prospective observational study, collecting clinical, biochemical, and endoscopic data from adult patients (n > 100) with moderate to severe UC who began MIRI treatment in our tertiary referral center in Munich, Germany. The primary endpoints were clinical remission, defined as a Clinical Activity Index (CAI, Lichtiger score) <4 and endoscopic remission, defined as an endoscopic Mayo score ≤1 at 12 months. Secondary outcomes included monthly (1-4 mo) and bimonthly (6-12 mo) trends in fecal calprotectin levels, CAI scores, urgency numeric rating scale (NRS), frequency of re-induction therapy (300 mg every 4 weeks for 3 doses), and steroid discontinuation during the observation period. Adverse events were systematically recorded. All statistical analysis was performed by SolidPulse Software in Phyton using pandas, scipy and statsmodels. This report presents the first key results from patients who have completed at least 6 months of treatment.

Results

To date, 73 patients have initiated MIRI therapy as approved; none have discontinued treatment. Of these, 55 patients have reached the 6-month follow-up. These 55 had a median disease duration of 11 years (range 3–43), and 55% were female. All 55 patients had been exposed to three or more advanced therapies before starting MIRI, and 23 patients (42%) received MIRI concomitantly in combination with another targeted therapy. Among the 55 patients, 29 (53%) had previously lost response to ustekinumab (90 mg every 8 weeks), and 19 (35%) were on concomitant corticosteroids at the start of MIRI therapy. At baseline, 36 patients had a Mayo endoscopic score of II or III, and 19 had a score of 0 or I.
Main results:

• The rates of clinical remission (CAI <4) increased from 36% (30/55) at baseline to 42% (23/55) at 1 month (p=0,6), 40% (22/55) at 2 months (p=0,8), 49% (27/55) at 3 months (p=0,09), 58% (32/55) at 4 months (p=0,008), and 58% (32/55) at 6 months (p=0.008, McNemar test).
• Median urgency NRS scores improved from 5 (range 0–10) at baseline to 1 (range 0–9) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Median calprotectin decreased from 460 (range 20–2100) at baseline to 75 (range 20–2100) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Among the 29 patients with prior ustekinumab use, clinical remission increased from 41% (12/29) at baseline to 55% (16/29) at 6 months, though this change did not reach statistical significance (p = 0.3, McNemar test), possibly due to the low number of patients.

Conclusion

Mirikizumab demonstrated clinical effectiveness and was well tolerated in a real-world UC cohort, including patients with longstanding disease and multiple prior treatments with advanced therapies.

References

1) D’Haens G, Dubinsky M, Kobayashi T et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. NEJM. 2023; 388: 2444–2455.
2) Dubinsky MC, Clemow DB, Hunter Gibble T et al. Clinical effect of mirikizumab treatment on bowel urgency in patients with moderately to severely active ulcerative colitis and the clinical relevance of bowel urgency improvement for disease remission. Crohn's Colitis 360. 2023; 360: 1–13.

Disclosure

This work has been funded by a grant from Eli Lilly

Introduction

Although CADe/x systems increase colorectal polyp detection, their ability to predict histological diagnosis is limited.

Aims & Methods

The aim of this study is to determine which factors related to morphology, histology and the image characteristics are associated with histology prediction by PolyDeep, a CADe/x system.
For this analysis, 5546 still images of colorectal polyps collected in PIBAdb database (https://www.iisgaliciasur.es/home/biobanco/colorectal-polyp-image-cohort-pibadb/?lang=en) were used. The images were obtained from videos recorded by endoscopist. Each image was associated with the endoscopy description (morphology, size), the final histology diagnosis and the characteristics (size, area) related with the Red, Green and Blue model (RGB model) and the Hue, Saturation and Value model (HSV model). Finally, the Convolutional Neural Network (CNN) determined the probability a polyp was classified as neoplastic lession (adenomatous, Traditional Serrated Adenoma,TSA, Sessile Serrated Lession, SSL). We determined Polydeep classified lesions as neoplastic if the probability was ≥0.5. We performed three analysis: (1) linear multiple regression in order to determine which variables are associated with the probability of classification as neoplastic lesions. (2). A multivariate logistic regresion analysis to define the variables associated with the classification as a neoplastic lesions. (3) A multivariate logistic regression to establish which variables are associated with missclassification of polyps. We use the R software for statistical computing.

Results

PolyDeep classified 84,51% of the lesions as neoplastic lession and managed to correctly classify 85.02% of the evaluated polyps (92.8% adenomas, 82.5% TSA, 84.2% SSL and 51.6% hyperplastic). The R² in the multiple linear regression is the 0.3655. The model associated to the neoplastic diagnosis has an Akaike Information Criterion (AIC) of 3363.3 and the model associated with missclassification, has an AIC of 3547.5. The variables associated to each regression model showed in the attached table.

Conclusion

The results obtained in this study allow us to establish strategies to improve Polydeep predicted histological diagnosis.

Introduction

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Histological outcomes and the immune landscape were assessed in an UC patient cohort at baseline and after 8 weeks tofacitinib.

Aims & Methods

In this prospective study, 40 patients with moderate to severely active UC received tofacitinib 10 mg twice daily for 8 weeks. Clinical, endoscopic and histological outcomes were assessed at baseline and week 8 and colon biopsies were stained for JAK1-3, Tyrosine kinase 2 (TYK2) and Signal transducer and activator of transcription (STAT) 1-6 total protein expression using immunohistochemistry (IHC). Histological remission was defined as a Robarts Histopathology Index (RHI) ≤3 points without mucosal neutrophils and histological response as 50% decrease in RHI compared to baseline. Response was defined as histological remission and endoscopic Mayo score (EMS) ≤1 (histo-endoscopic mucosal improvement). Biopsies were scored by a blinded pathologist. Whole slide images with multiple biopsies per patients were stained using IHC, analyzed using automated cell detection (QuPath) and quantified in percentages by dividing the number of positive stained cells by the total number of cells on the slide. Outcomes were compared between responders and non-responders (NR).

Results

Out of 40 patients, 26 (65%) had severe endoscopic disease (EMS 3) with a median RHI of 14. Thirty-one patients (78%) had failed prior anti-Tumor Necrosis Factor (anti-TNF) agents and 18 (55%) failed vedolizumab. At week 8, 23 patients (58%) achieved histological remission, 34 (85%) histological response and 15 (38%) histo-endoscopic mucosal improvement. A significant decline in RHI compared to baseline was observed after 8 weeks both in responders (14 vs 0, p<0.001) and NR (15 vs 6, p=0.002). In the entire cohort, total STAT1 (p<0.001), STAT3 (p=0.002) and STAT5 (p=0.026) expression significantly decreased after 8 weeks treatment compared to baseline, which was not different between responders and NR (Table). However, responders to tofacitinib expressed significantly lower total STAT1 levels compared to NR at 8 weeks (p<0.001). Likewise, JAK2 (p=0.008) and total STAT2 expression (p=0.004) were significantly lower in responders compared to NR at 8 weeks, although no significant decrease compared to baseline was observed. A trend towards lower baseline JAK1, JAK2 and total STAT4 expression and higher total STAT6 expression was seen in responders compared to NR.

Conclusion

Tofacitinib resulted in histological response in the majority of UC patients and led to a substantial decline of total STAT1, STAT3 and STAT5 expression both in responders and NR. Yet, after 8 weeks significantly lower total STAT1 levels were observed in responders compared to NR. Responders tended to express lower JAK1, JAK2 and total STAT4 and higher total STAT6 levels at baseline.

Disclosure

This study was funded and supported by Pfizer.