I-CARE: An imminent European success story in the field of IBD
Laurent Beaugerie, ClinCom Member
The efficacy profile of IBD drugs is rapidly characterised by pivotal randomised controlled trials, but the safety profile of both old and new IBD drugs can only be established after years or decades of post-approval use. This is particularly true for relatively rare events, such as immunosuppression-related cancers. Clinical trials, meta-analyses and safety-dedicated registries are in general underpowered to evaluate the impact of IBD therapies on the risk of development of particular cancers. Data on clinical activity and phenotype of IBD are missing from nationwide administrative health databases, making it impossible to distinguish between the respective effects of IBD drugs and IBD activity on the risk of outcomes of particular interest, such as lymphomas.
Therefore, ambitious investigator-initiated projects are essential to fill in the gaps in knowledge on the risk-benefit profiles of IBD drugs. The CESAME project was a significant example in the field. In this nationwide French prospective cohort, almost 20,000 patients, a third of whom had been exposed to thiopurines, were followed up for a median of 2.5 years in the early 2000s. The major result of the CESAME project was the characterisation of the excess risk of lymphoma associated with the use of thiopurines, particularly in older men and EBV-seronegative patients. This important result has been taken into account in the most recent ECCO Guidelines.
The CESAME project had notable limitations, however. Cancers were the sole outcomes of interest. Data on the dose and duration of IBD drugs prior to cohort enrolment were lacking. There was also no prospective assessment of IBD activity, though this activity may have an impact on the risk of some cancers and infections.
The I-CARE (IBD CAncer and seRious infections in Europe) project was initiated in 2010 after drawing lessons from the experience of the CESAME cohort project. The major objective of I-CARE was to assess prospectively the safety profile of anti-TNFs (with respect to cancers, especially lymphomas, and serious infections), alone or in combination with thiopurines, among IBD patients. The I-CARE project was also designed to be able to investigate the impact of IBD drugs on IBD clinical activity and disease progression. If this goal can be achieved, it is likely that clinicians as well as healthcare authorities will use data from I-CARE to attempt to achieve the best benefit-risk ratio in the long-term management of IBD.
From March 2016 to April 2019, more that 10,000 patients were enrolled in the I-CARE project by some 500 IBD specialists from 15 European countries (Belgium, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, the Netherlands, Poland, Portugal, Spain, Sweden and United Kingdom). Patients reported on a monthly basis, via a dedicated platform, exhaustive information on clinical IBD activity, IBD treatment details and changes, and any cancer, serious infection or hospitalisation. Baseline characteristics of patients (IBD phenotype and past history, and IBD treatment at entry and prior to enrolment) will be reported in the first I-CARE original paper, which has just been submitted for publication.
The follow-up of the last patient expired at the end of March 2022. The majority of the patients completed the 3-year expected follow-up time, and many of them agreed on a voluntary basis to extend their individual follow-up time to March 2022, the date at which the follow-up of the last enrolled patient expired.
Twelve years after the design of the study, the time for science has come, and hopefully you will see the first major results of the study at the 2023 ECCO Congress!