The BIOCYCLE project has now been ongoing for over 4 years. This project, funded by the European commission under the Horizon 2020 program, aims at exploring different aspects of the question of treatment de-escalation in moderate-severe Crohn’s disease, first requiring a combination therapy with anti-TNF and antimetabolites to control the disease. Once the disease has been stabilized, an unsolved question is to whether it is possible to de-escalate therapy. This question is important for several reasons including safety, tolerance, quality of life or costs to name the most prominent. Biocycle includes a randomized three arms, controlled clinical trial, called SPARE, on 200 patients in 6 European countries (France, United Kingdom, Belgium, Sweden, The Netherlands and Germany) and Australia, several patients and health care providers’ surveys in Europe and the USA, a biomarker research program and pharmaco-economic analysis. ECCO is mainly involved in the monitoring of the project (through the Sci Com and the Clin Com) and is the work package leader for dissemination of the results. Biocycle is a 7.5 years-long project and has been launched in April 2015.
The global aim of Biocycle is to try and bring an integrated multidimensional and tailored response to this difficult question of treatment de-escalation in Crohn’s disease, also taking into account patients’ preferences and perspectives.
What has been achieved so far?
All work packages have now started and made progress.
The SPARE clinical trial is progressing well. The inclusions have been closed in March 2019, reaching 252 screened patients and 211 randomized patients. Around half of the patients have now finished the trial. The last patient will be out of the trial in March 2021. Therefore, we expect first results on the primary end points being available in the second half of 2021 and being presented at ECCO 2022. The Data safety monitoring board has noticed no new safety signal and has regularly confirmed that the trial could continue unchanged. The relapse rates observed so far in the three arms are close to the initial hypotheses.
The health care providers’ and patients’ surveys, coordinated by the CCFA in the USA and by the patients’ association AFA in France, with the help of ECCO, and in which participated more than 400 patients and close to 300 doctors, are finished and results have been presented at ECCO congress 2017 and 2018. The manuscript summarizing the most important results are currently submitted for publication.
The biological samples collected at baseline and different time points of follow up include blood DNA and RNA, plasma, serum and stool. They are regularly transferred to the central biobank in Liège. From there some samples have recently been transferred to Oxford for a study of DNA methylation, miRNA, and glycomics. Other samples will be transferred to Tel Aviv early 2020 for a first set of analyses of infliximab and anti-infliximab antibodies levels. Proteomic studies have already started in Liège and a first set of markers associated with the risk of relapse has been identified through mass spectrometry in a pilot cohort and will now be tested in the SPARE baseline samples.
The pharmaco-economic work package led by Gothenburg University has started and a theoretical pharmaco-economic model for the cycling of Immunomodulators or biologics has been generated based on a Markov-type decision tree model. The results of this model have been presented at the ECCO 2019 congress and published in the following months in the Journal of Crohn and Colitis.
The final aim of Biocycle is to generate a multidimensional integrated tool to help making decision as far as treatment withdrawal and cycles in Crohn’s disease and more broadly in IMIDs. To this end, the consortium is working on a clinical decision support system (CDSS). A publication on this concept has been published in the Journal of Crohn and Colitis in 2018 and the consortium is currently working on a first version of the CDSS tool. This tool will be tested by a small number of IBD clinicians on a first series of patients and will be optimized by this first experience, also using artificial intelligence. It will later be fed by the results of the SPARE clinical trial and the other BIOCYCLE work packages.
The third administrative and scientific report is currently being prepared and will be submitted to the European commission before the end of November 2019.
For more information, see: the BIOCYCLE website: http://biocycle-project.eu/; EU reference: grant agreement No 633168 – BIOCYCLE (PHC-13-2014).