Research Projects

João A. Cunha Neves, MD*; Joana Roseira, MD, PhD student*; Helena Tavares de Sousa, MD, PhD student*
*Gastroenterology Department – CHUA – Centro Hospitalar Universitário do Algarve, Portimão, Portugal

Rational: Vedolizumab and ustekinumab are considered the top-tier safest biologic medications for inflammatory bowel disease (IBD). Both these drugs are important therapeutic options in a particular pool of patients not suitable to anti-TNFα drugs, namely those with present or previous malignancies and elderly. Once vedolizumab failure is established, most patients will be offered ustekinumab therapy, and robust evidence on efficacy and safety of this second-line treatment regimen in this setting is lacking.

Research hypothesis:
1) Efficacy of ustekinumab will be less impacted by vedolizumab exposure compared to anti-TNFα exposure.
2) Safety profiles will be similar between ustekinumab after vedolizumab and ustekinumab after anti-TNFα.

Primary objective: To assess clinical remission of ustekinumab as second-line treatment after failure of vedolizumab in anti-TNFα naïve patients.

Secondary objectives:
1) To assess the durability of ustekinumab as second-line treatment after vedolizumab failure versus after anti-TNFα failure.
2) To assess objective (decrease in biomarker) efficacy of ustekinumab as second-line treatment after failure of vedolizumab in anti-TNFα naïve patients.
3) To assess endoscopic efficacy (response and remission) of ustekinumab as second-line treatment after failure of vedolizumab in anti-TNFα naïve patients.
4) To compare the efficacy of ustekinumab as second-line treatment after vedolizumab failure versus after anti-TNFα failure.
5) To assess the safety profile of ustekinumab either after vedolizumab or after anti-TNFα.

Every IBD centre with a retrospective database or list of adult IBD patients, with easily retrievable data and a low risk of missed cases, who are willing to provide information about their patients.

Prof. Gianluca Pellino, Dr. Alice Gori, Prof. Matteo Rottoli, Mr. Valerio Celentano , Salvatore Leone , Prof. Antonino Spinelli, Prof. Giuseppe S. Sica, Prof. Gianluca Sampietro, Prof. Francesco Selvaggi

Purpose
The purpose of the study is to obtain information about fertility pregnancy outcome of patients undergoing surgery for CD and UC. The primary aim is the ability to become pregnant. Secondary aims include factors associated with pregnancy, attempts, and mode of delivery. The effects of treatments and disease activity on fertility and outcome of pregnancy will be assessed. A cohort of patients who did not undergo surgery will be established for comparison. The questionnaire for patients contains an open text part, in which patients will be able to report any personal experience.

Outcome measures
Primary endpoint:

• proportion of patients who have managed to become pregnant.

Secondary endpoints:

• number of pregnancy attempts;
• time interval between pregnancy attempts and pregnancy (months);
• way pregnancy was achieved (need for gynaecological consultation, intervention);
• number of miscarriages/interruptions of pregnancy;
• necessity to discontinue medical treatment during pregnancy;
• disease recurrence rate during pregnancy;
• type of delivery (natural vs. caesarean section).

Colorectal surgery centers from any country with high IBD incidence (>/= 50 patients in the study period) will be eligible for the study. Each center will create a work team composed by: 1 Hospital lead/Principal Investigator, 3 collaborators, 1 data validator.

Inclusion criteria

• All female patients who underwent surgery for CD or UC before the age of 36 (at the time of the study) from 2000 to 2022.
• Diagnosis of Crohn's disease or ulcerative colitis
• Ability to understand the study
• For the non-surgical group, all patients who received treatment for CD or UC from 2000 to 2022 will be considered

Exclusion criteria

• ˂ 18 years of age at the time of the study
• Lack of diagnostic certainty of Crohn's disease or ulcerative colitis

Department of medical sciences, University of Turin, Turin, Italy.

Internal medicine, Department of internal medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy

The main objective of this study is the evaluation of the incidence rate of colitis remission basing on the CTCAE scale within 12 months.

Secondary objectives of the study are:
1. to evaluate the clinical remission with specific colitis CTCAE scale and with the Physician Global Assessment (PGA)
2. to assess endoscopic and histological healing, whether the endoscopic examination is repeated after the diagnosis.
3. to evaluate the fatality rate and the causes of death among these patients; these will be calculated by gathering information on the modality of death during the follow-up period.
4. to identify all the different patterns of this kind of enterocolitis, by collecting data on the localisation (colonic, ileal, ileo-colonic), the endoscopic (ulcerative, oedematous) and histological features (granulomatosis, crypt abscesses, etc.), and their related prognosis.
5. to describe any epidemiological features of CIC such as male/female ratio, mean age, smoking habits, previous oncological treatments, tumour localisation and will assess any predictors of colitis development or clinical response to colitis-related treatment.

• Any IBD, gastroenterological, oncological, or internal medicine center dealing with ICIC that are willing to provide data with an (expected) date of delivery of 31^st December 2022 for the retrospective part and to enroll prospectively patients from January 2023 to December 2023 and follow them up for 12 months (prospective part)
• All centers that are willing to ask for approval to their local ethics committee, according to their local jurisdiction; each center will be responsible for the submission to the local ethics committee

The primary aim of the study is to evaluate the prevalence of AP in IBD patients.

Secondary aims include:

• To investigate the aetiology of AP in IBD patients
• To investigate the relationship between IBD medications and AP
• To investigate the relationship between IBD medications and CPEE
• To define the role of different imaging modalities in improving diagnosis of pancreatic abnormalities
• The explore the clinical outcome of specific pancreatic manifestations

• Each IBD center which maintain a prospective or retrospective list of adult IBD patients, with easily retrievability of data and a low risk of missed cases, who are willing to provide information about their patients with one or more pancreatic disorders

The aim of this study would be to determine the safety of TOFA administration in the weeks before total colectomy for medically refractory UC.

In addition, a subsequent analysis on potential predictive factors of adverse outcomes within TOFA group of treatment might provide precious information on safe patient selection.

• IBD centres with the possibility to retrieve data on UC patients undergoing colectomy and the necessary information in the perioperative period
• IBD centres who are willing to fill out an electronic clinical research form (eCRF) through REDCap® software for all included patients.
• IBD centres who are willing to verify themselves if approval by their local ethical committee and informed consent of the patient is mandatory in their jurisdiction for a retrospective non interventional study. If so, the IBD centre will be responsible for the submission to the local ethical committee as well as collection of the informed consent

• IBD centres which kept track of Crohn’s patients that underwent ileocecal resection over at least the past decade
• IBD centers who are willing to fill out completely and correctly an electronic clinical research form (eCRF) through REDCap® software for all included patients
• IBD centers who are willing to verify themselves if approval by their local ethical committee and informed consent of the patient is mandatory in their jurisdiction for a retrospective non interventional study. If so, the IBD center will be responsible for the submission to the local ethical committee as well as collection of the informed consent. As mentioned, the study was already approved by the Ethical Committee of University Hospital Ghent (Belgium) on 05/03/2021
• IBD centres who are willing to do everything to avoid missing data as much as possible by contacting patients, colleague gastroenterologists, general practitioners and any other physicians in charge of the patient

• To determine the optimal timing of surgery following SARS-CoV-2 infection;
• Determine assess key global surgical indicators, such as postoperative mortality.

• In order to achieve the above aims, this study will include all patients undergoing surgery
  with a preoperative, postoperative or no SARS-CoV-2 infection.
• All hospitals are eligible
  to participate, regardless having admitted SARS-CoV-2 infected patients or not.

Full manuscript: 

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy. Kopylov U, Hanzel J, Liefferinckx C, De Marco D, Imperatore N, Plevris N, Baston‐Rey I, Harris RJ, Truyens M, Domislovic V, Vavricka S, Biemans V, Myers S, Sebastian S, Ben‐Horin S, González Lama Y, Gilletta C,  Shitrit Ariella B-G, Zelinkova Z, Weishof R, Storan D, Zittan E, Farkas K, Molnar T, Franchimont D, Cremer A, Afif W, Castiglione F, Lees C, Barreiro‐de Acosta M, Lobaton T, Doherty G, Krznaric Z, Pierik M, Hoentjen F, Drobne D. AP&T https://doi.org/10.1111/apt.15784