Introduction

Interleukin (IL) inhibitors are monoclonal antibodies that have been shown to be effective in inducing and maintaining remission in moderate to severe ulcerative colitis (UC).
Ustekinumab (UST) was approved in the EU for the treatment of UC in 2019 and binds specifically to the p40 protein subunit of IL-12 and IL-23. Mirikizumab (MIRI) was approved 4 years later and selectively binds to the p19 subunit of the IL-23 cytokine. By binding to the IL subunits, the interaction with the IL-23 receptor is inhibited.
In this study, we compared the response rate to induction therapy with UST and MIRI in patients with moderately to severe UC.

Aims & Methods

All patients with active UC who began induction therapy with UST or MIRI at our outpatient clinic between 2019 and 2024 were analyzed retrospectively with a follow-up period until April 2025. Patients who received the IL-23 inhibitor due to a disease other than UC or following a prednisolone therapy exceeding 20 mg and patients with pouchitis were excluded from the study.
We determined the response to IL-23 therapy 8 to 24 weeks after the start of treatment and documented this either as clinical remission (Mayo-Score ≤1), improvement (Mayo-Score reduction by at least 3 points), inadequate response (Mayo-Score reduction between 0 and 2) or no response (lack of benefit, switch to another medical class or colectomy).
We examined the levels of calprotectin in the stool 0 to 24 weeks before the start of IL-23 therapy up to 24 weeks after initial administration.
Our study included 40 patients treated with UST and 23 patients treated with MIRI, in the latter group 26% have previously been treated with UST. Patients in both groups were similar in age (mean age, 47.75 vs. 44.59 y; P 0.28), gender, disease duration (mean duration, 11 vs. 9 y; P 0.32), and extent of disease (pancolitis, 40% vs. 48%).

Results

After completion of induction, 25% in the UST group and 57% in the MIRI group reached clinical remission. MIRI after UST achieved clinical remission in 67%. Improvement was shown in 20% vs. 30%, UST vs. MIRI. For UST, 5% were non-responder. For MIRI, no non-responder was noted. In general, the difference between the pre- and post-induction Mayo-Score is significantly higher for MIRI, indicating a better response to the newly started drug (mean Mayo-Score difference, UST vs. MIRI, 2.95 vs 4.5; P 0.0003)
The mean calprotectin level before treatment was not significantly different (mean calprotectin, UST vs. MIRI, 1652 vs. 2452 mg/kg; P 0.17). The post-treatment calprotectin level was significantly higher for UST vs. MIRI (mean calprotectin, 1092 vs. 278 mg/kg; P 0.0083).

Conclusion

Mirikizumab is an effective induction treatment for patients with active ulcerative colitis, including those who previously did not respond adequately to Ustekinumab therapy.

Introduction

Watch-and-Wait is an increasingly recognized non-surgical management option for rectal cancer patients achieving a clinical complete response (cCR) following neoadjuvant therapy. This approach aims to preserve organ function by avoiding surgery, but necessitates vigilant endoscopic surveillance, to detect local tumor regrowth¹ (LTR). The specific endoscopic features associated with regrowth remain incompletely defined.

Aims & Methods

We performed a retrospective analysis of patients monitored under the Watch-and-Wait program at Karolinska University Hospital², focusing on the endoscopic characteristics of LTR. As of December 2023, 145 patients who met the criteria for clinical complete response (cCR) were included.
The neoadjuvant treatment consisted of chemoradiotherapy (CRT) in 16 patients (11%), short course radiotherapy (SCRT) + chemotherapy in 69 patients (47.6%) and SCRT alone (5 x 5 Gy) in 60 patients (41.4%). The median age of the patients was 66 years (range 29-94), with 61.4% being male. The initial tumor stage was T1/T2 in 42 patients (29%) and T3/T4 in 103 patients (71%). The nodal stage was N0 in 35 patients (24%) and N+ in 110 patients (75.9%). The median follow-up period was 29 months (range 3-102 months).
Patients were monitored with rectal digital exams, flexible endoscopy, CEA measurements, and MRI every 3 months for 2 years, and then every 6 months thereafter. During endoscopy, narrow-band imaging (NBI) and NICE classification³ was utilized.

Results

Out of the 145 patients, 28 (19.3%) experienced LTR as of December 2023. The median time from the completion of radiotherapy to regrowth was 9 months (range 3-20 months). Regrowth was detected intraluminally by endoscopy in 23 patients (82.1%), while in 5 patients (17.9%), regrowth was detected on MRI but was not visible intraluminally.
The most common endoscopic features of regrowth included a NICE 3 pattern (n=16) and contact bleeding (n=16). Additional findings included polypoid tissue (n=13), ulceration (n=10), irregular surface (n=9), fibrin cover (n=9), stenosis (n=6), and submucosal nodules (n=5).

Conclusion

As regrowth occurs in at least one of five patients and most commonly with intraluminal findings, this study highlights the importance of meticulous endoscopic follow-up. Contact bleeding and NICE type 3 lesions observed with narrow-band imaging (NBI) were key endoscopic findings in patients with tumor regrowth, while polypoid lesions were observed in less than 50%. Combining endoscopic assessment with other modalities, such as MRI, is essential, as regrowth may be undetectable endoscopically in a proportion of patients.

References

1. Cerdan-Santacruz C, Vailati BB, Sao Juliao GP, Habr-Gama A, Perez RO. Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short. Tech Coloproctol 2023;27(1):1-9. DOI: 10.1007/s10151-022-02654-5.
2. Nilsson PJ, Ahlberg M, Kordnejad S, Holm T, Martling A. Organ preservation following short-course radiotherapy for rectal cancer. BJS Open 2021;5(5). DOI: 10.1093/bjsopen/zrab093.
3. Hamada Y, Tanaka K, Katsurahara M, et al. Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study. BMC Gastroenterol 2021;21(1):336. DOI: 10.1186/s12876-021-01898-z.

Disclosure

Stephan Haas (SLH) has received speaker's honoraria from Santax Medico, Tillotts Pharma, Lilly, Mediahuset, and Johnson & Johnson.

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.