Letter from the ECCO President

Julián Panés, ECCO President

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Julian PanesJulián Panés  ©  ECCO

Dear ECCO friends,

We are witnessing an exciting period in the development of new therapies for Inflammatory Bowel Diseases. New therapeutic targets, and new classes of drugs, are being integrated into our therapeutic armamentarium. However, when we consider the proportion of patients who respond to induction therapy and, among those, the fraction who achieve remission during maintenance, the percentage of initially treated patients in whom the disease is satisfactorily controlled over one year does not exceed 15%30%.

In the process of drug development, constraints from regulatory bodies and pressure from marketing departments may lead to trial designs aiming to show that the new drug can treat any patient with Crohn’s Disease or Ulcerative Colitis, irrespective of phenotype, disease course or prior drug exposure.

IBD has proved to be a particularly complex condition due to the number of factors interacting in its pathogenesis, where the homeostasis that controls the local physiological low-grade inflammation is disrupted by multiple and poorly understood interactions among environmental, genetic, microbial and immune factors. Key to the understanding of a multifaceted complex system such as IBD is the characterisation of the interactions and causative relationships between all the components. Experimental approaches to putatively relevant targets that rely on in vitro and in vivo systems still make sense, but currently these approaches are still being implemented in a biological vacuum, i.e. they are carried out using reductionist systems that do not take into account the complex biological reality that goes on in the patients, both as a group and as individual subjects.

Biological complexity cannot be meaningfully tackled with single-target, single-solution systems. Rather, each pathogenic component needs to be understood in its totality, followed by integration of each totality into a comprehensive unifying network, i.e. the IBD interactome. This is what systems biology can do for IBD, and coupling translational system biology approaches of target identification and drug discovery with early clinical trials will bring significant advances in overall therapy, and in our understanding of disease, the discovery of biomarkers and personalised medicine. As clinicians we should make every possible effort, in our investigator-initiated studies and in our collaborations with the industry, to foster clinical research in this direction, and the industry should understand the any advance in the area of predictors and precision medicine is what will make a difference for their product, a difference that will considerably surpass what marketing departments can achieve.

Posted in ECCO News, Letters from the ECCO President, Volume 12, Issue 4