The primary objective of I-CARE is to assess prospectively the presence and the extent of safety concerns (cancers (especially lymphoma) and serious infections risks) for anti-TNF or other biologic alone or in combination with thiopurines among IBD patients. Safety profile of all steroids formulation will also be analysed. We will stratify the risk of cancers and serious infections according to IBD phenotype and disease activity (clinical, radiologic and endoscopic).
The four main secondary objectives of the I-CARE project are:
- To investigate prospectively the impact of anti-TNF or other biologic based strategies on the natural history of IBD and their potential for disease modification by collecting validated surrogate markers such as mucosal healing and disease complications such as bowel damage (strictures, fistulas, abscess), surgeries, and hospitalizations.
- To assess the evolution of PROs on a yearly basis and the impact of anti-TNF agents or other biologic on PROs in IBD
- To evaluate the benefit-risk ratio of strategies based on an earlier and wider use of anti-TNF or other biologic therapy for IBD
- To assess the healthcare costs and cost-efficacy of current therapeutic strategies in IBD.
This is a European prospective longitudinal observational multicenter cohort study. A total of 16 countries will participate. However, the final list will be confirmed upon confirmation of the country capacity by the National Coordinator: Belgium, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Poland, Portugal, Russia, Spain, Sweden, Switzerland, and UK. In France, the Investigators will be selected by the National Coordinators (Vered Abitbol and Stéphane Nahon) from the members of EPIMAD, ANGH and CREGG, as well as the GETAID.
Study duration: 6 years
- Three-year inclusion period (March 2016 to December 2018 for group 1 to 5, until March 2019 only for group 6)
- Three-year follow-up period for all patients and three additional years for patient on voluntary basis and can be stopped by patient at any time.
Sample size, number of investigators, number of patients per investigator, participating countries
Calculation of sample size was made based on the primary objective of ICARE. We estimated that a minimum of 47,000 patient-years are needed for the study to have a statistical power of 80% to detect a lymphoma hazard ratio of at least 3.5 in the groups of patients receiving thiopurines, either alone or in combination with anti-TNF, vedolizumab or ustekinumab, relative to patients not receiving thiopurines (i.e. receiving anti-TNF alone or no IS). The final patient population will be up to 17,600 and the follow-up duration for each patient will be 3 years. If necessary, we will consider extending the inclusion duration and/or the follow up of patient over 3 years to reach our objective of 47,000 patients-years. A total of up to 800 investigators working in reference centers in IBD will be recruited via ECCO and National Coordinators.
Investigators will be all European gastroenterologists from the participating countries voluntary for participating in the study on an unpaid basis, and accepting to provide phone number and e-mail address for the purpose of the study.
Each investigator will include a total of 27 inpatients or outpatients that he personally manages for IBD, matching the inclusion criteria and stratified according to the exposure to immunosuppressive therapy at inclusion:
- Group 1: 5 patients who have no ongoing immunosuppressant and biologic agent at inclusion in I-CARE study (all previous medication accepted) (all 5-ASA and steroids formulations are permitted)
- Group 2: 5 patients receiving thiopurines alone
- Group 3: 5 patients treated with anti-TNF therapy alone without any concomitant immunosuppressant
- Group 4: 5 patients treated with anti-TNF therapy in combination with thiopurines or methotrexate
- Group 5: 2 patients: For investigators following IBD patients treated with vedolizumab, a 5th Group is constituted with enrollment of one patient treated with vedolizumab alone (without any concomitant immunosuppressant) and one patient treated with vedolizumab in combination with thiopurines or methotrexate.
- Group 6: 5 patients treated with ustekinumab with or without any concomitant medications. (optional)
- OPTIONAL: After inclusion of 27 patients, each investigator can enroll up to 100 patients (not mandatory) unlimited number of patients per group :
- Group 1: patients who have no ongoing immunosuppressant and biologic agent at inclusion in I-CARE study (all previous medication accepted) (all 5-ASA and steroids formulations are permitted)
- Group 2: patients receiving thiopurines alone
- Group 3: patients treated with anti-TNF therapy alone without any concomitant immunosuppressant
- Group 4: patients treated with anti-TNF therapy in combination with thiopurines or methotrexate
- Group 5: patients: For investigators following IBD patients treated with vedolizumab, a 5th Group is constituted with enrollment of five patients treated with vedolizumab alone (without any concomitant immunosuppressant) and five patients treated with vedolizumab in combination with thiopurines or methotrexate.
- Group 6: patients treated with ustekinumab with or without any concomitant medications. (optional)
Patient with an established diagnosis of Crohn’s disease, ulcerative colitis or IBD, unclassified made at least 3 months earlier based on usual radiological, endoscopic or histological criteria.
Patient 18 and older accepting to sign the informed participating consent form, stating that he accepts to provide personal details (mobile and home phone number, e-mail address), to complete the e-PRO as required and to be contacted by a Study Coordinator and his gastroenterologist for the purpose of the study during the entire study period and during follow up if required.
- Patient unable to sign the informed consent form
- Patient with no regular access to internet
- Patient refusing to sign the informed consent form
- Treatment at entry in the study with an immunomodulator different from thiopurines and methotrexate (cyclosporine, tacrolimus, mycophenolate mofetil, etc.)
- Patient previously enrolled in a Randomized Clinical Trial (If the investigational product received was blinded, and if the treatment is unknown at time of enrollment in I-CARE)