Research group

This will be a Panhellenic multicenter study under the auspices and coordination of EOMIFNE.

Study principal investigator: Evanthia Zampeli, GI-UNIT, 3 RD Academic Dpt. of Internal

Medicine, National & Kapodistrian University of Athens, Sotiria Hospital

Study co-ordinator: Georgios Kokkotis, GI-UNIT, 3 RD Academic Dpt. of Internal

Medicine, National &Kapodistrian University of Athens, Sotiria Hospital.

Study participants: All the investigators from IBD centers in Greece, who will respond to the invitation call from EOMIFNE.

Introduction

Crohn's Disease and Ulcerative Colitis, are chronic, relapsing inflammatory disorders of the gastrointestinal tract associated with substantial morbidity, impaired quality of life and healthcare utilization. Despite the expansion of advanced therapies over the past two decades, many patients continue to experience inadequate disease control and corticosteroid dependence, that leads to hospitalization, and surgery due to cumulative structural complications.¹

Selective inhibition of the interleukin-23 (IL-23) pathway poses as a promising therapeutic advance in IBD. IL-23 plays a pivotal role in intestinal immune dysregulation through maintenance of pathogenic Th17-mediated inflammatory responses. The monoclonal antibodies guselkumab, mirikizumab, and risankizumab target the p19 subunit of IL-23, and have been proven effective in inducing and maintaining remission in moderate-to-severe IBD, with favorable safety profiles. However, real-world evidence regarding anti-IL-23 treatment response, as well as long-term treatment continuation, remains limited.²

Contemporary management of inflammatory bowel disease (IBD) has shifted from symptom-based care, toward a proactive treat-to-target strategy, focused on objective disease control. STRIDE-II recommends regular assessment of inflammatory markers and adjustment of therapy toward predefined targets, including clinical remission, biomarker normalization, endoscopic healing, and when feasible, transmural healing. Achieving these targets has been associated with improved long-term outcomes, including reduced corticosteroid use, hospitalization, surgery, and disability.³

Effective implementation of treat-to-target strategies requires reliable and non-invasive monitoring tools. Although endoscopy remains the reference standard, its invasiveness and limited feasibility for frequent monitoring restrict routine use. Intestinal ultrasound (IUS) has emerged as a valuable point-of-care modality, enabling real-time assessment of bowel inflammation and transmural disease, without radiation exposure or the need for bowel preparation. Increasing evidence suggests that IUS can facilitate early detection of treatment response and support personalized therapeutic decisions within modern IBD care.³

Additionally, the identification of predictors of response to IBD therapies is a major unmet need in contemporary clinical practice. Early identification of clinical, biochemical, endoscopic, and imaging predictors associated with treatment success, may enable a more individualized therapeutic approach, optimizing treatment selection, limiting unnecessary exposure to ineffective therapies, and improving long-term outcomes. Such strategies are fundamental to the transition toward personalized medicine in IBD, where treatment decisions will be guided by patient-specific disease characteristics and the  response to treatment accurately predicted.⁴

Finally, a significant unmet need is the effective pharmacological treatment of perianal Crohn’s Disease. With infliximab being the only approved agent for the treatment of active perianal disease, those patients regularly experience relapses that cause significant deterioration in their quality of life.⁵

There are still limited prospective studies evaluating how anti-IL-23 therapies perform within a structured treat-to-target framework, incorporating serial intestinal ultrasound assessments. Understanding the temporal relationship between clinical response, biomarker normalization, and sonographic improvement may help refine monitoring algorithms, identify early predictors of response, and optimize treatment strategies in routine practice.

The present prospective cohort study aims to evaluate patients with IBD, commencing therapy with anti-IL-23 agents (guselkumab, mirikizumab, or risankizumab) in real-world clinical practice. The study will record the treatment continuation rates, assess clinical, biochemical, and sonographic outcomes over a 3-year period, will seek to identify predictors of response and record any adverse outcome. By integrating objective disease monitoring with contemporary biologic therapy, this study aims to generate real-world evidence regarding treatment effectiveness, early response assessment, and the role of IUS-guided management in modern IBD care. Identifying biomarkers associated with good treatment response will assist facilitate the transition toward personalized medicine in the treatment of IBD.

Methods

Study Design

Prospective, multicenter study in patients with Crohn’s Disease and Ulcerative Colitis, older than 16 years old, who initiate guselkumab, mirikizumab, or risankizumab. Each patient will be followed up for up to 3 years, or until treatment discontinuation, at specific time-points.

Outcomes

Primary outcome: Treatment persistence

Secondary outcomes: Clinical remission, corticosteroid-free clinical remission, endoscopic response, endoscopic remission, biochemical and sonographic response at 1, 2 and 3 years. Clinical and sonographic response after induction, at week 12. Recording of treatment intensification and re-induction rates and adverse outcomes.  Indirect comparison between the different anti-IL23 treatments. Effect of anti-IL23 treatment on perianal disease,  based on the need for repeat surgical intervention or treatment switch.

Outcomes definitions: The outcomes will be based on STRIDE-II³ and the Expert Consensus Statement of the IBUS Group⁶

	CD	UC
Clinical response	PROs reduction ≥ 50%
Clinical remission	PRO abdominal pain≤1, PRO stool frequency≤3	PROs=0
Endoscopic response	SES-CD reduction >50%	endo-MAYO reduction
Endoscopic remission	SES-CD ≤3 with "ulceration"=0	endo-MAYO=0
Sonographic response	BWT reduction >25% OR BWT reduction >2mm OR BWT reduction >1mm+color Doppler reduction
Sonographic remission	BWT ≤3mm + color Doppler=0
PRO: Patient Reported Outcome, BWT: Bowel wall thickness

 

Time-points

Week 0 (1^st induction dose), Week 4 (2^nd induction dose), Week 8 (3^rd induction dose), Week 12 (end of induction period), Week 24-28, Week 52, Week 104, Week 156

Data Collection

For each patient the following data will be collected:

Demographic (age, gender)

Biometric (weight, height)

Social (smoking habits)

IBD related history (type of disease, Montreal classification, age at diagnosis, surgical history, previous treatments, extraintestinal manifestations, concomitant treatments)

Disease activity (for Crohn’s Disease: PROs of abdominal pain and stool frequency, SES-CD, Rutgeert’s score; for Ulcerative Colitis: PROs of rectal bleeding, bowel movement and urgency, endo-MAYO, UCEIS; biochemical: fecal calprotectin, CRP, hemoglobin, albumin; for intestinal ultrasound: bowel wall thickness, color Doppler, bowel wall stratification)

Adverse events

Statistical analysis

Total count and percentages will be used to calculate the rates of the primary and secondary outcomes. For continuous variables that are normally distributed “Mean value” and “Standard Deviation”, while for those not normally distributed “Median” and “Range” will be calculated. Cox regression will be used to identify factors associated with the outcomes of interest. Time-to-treatment discontinuation will be evaluated using Kaplan-Meier plots, with comparisons performed using the long-rank test. A P-value=0.05 will be used as threshold of statistical significance. 

Bibliography

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3. Turner D., Ricciuto A., Lewis A., D’Amico F., Dhaliwal J., Griffiths AM., et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021;160(5):1570–83. Doi: 10.1053/j.gastro.2020.12.031.
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6. Ilvemark JFKF., Hansen T., Goodsall TM., Seidelin JB., Al- Farhan H., Allocca M., et al. Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement. J Crohns Colitis 2021;16(4):554–80. Doi: 10.1093/ecco-jcc/jjab173.