Predicting the Course of IBD: Light at the End of the Tunnel?

Abstract

Prognosis in Crohn’s disease (CD) and ulcerative colitis (UC) varies substantially between patients. Accordingly, no single treatment strategy will be suitable for everyone. ‘Top-down’ strategies inevitably overtreat patients destined to experience indolent disease (and risk unnecessary immunosuppression), whilst ‘step-up’ strategies expose patients with aggressive disease to avoidable disease-related morbidity. Accordingly, for personalised medicine to succeed in IBD, a reliable method of predicting prognosis is critical. In oncology, gene expression profiling enables reliable prediction of several aspects of tumour behaviour. Unfortunately, this technology has been less successful in other disease areas – often because heterogeneous cell populations are studied, producing gene signatures that simply reflect compositional differences in the starting material. This can be overcome by analysing purified cell populations. Previously, we discovered a prognostic gene expression signature in purified CD8+ T cells from patients with systemic lupus erythematosus and ANCA-associated vasculitis. We therefore investigated whether the same signature might exist in other relapsing-remitting diseases driven by immune responses to antigen, and detected an analogous signature in CD and UC. This signature was detectable from diagnosis, but did not correlate with contemporaneous clinical or biochemical data. A significant association with prognosis was detected in both UC and CD, with patients who were enriched for the signature (subgroup ‘IBD1’) experiencing a more aggressive disease course, characterised by frequent flares and a higher incidence of treatment failure. This suggests that gene expression profiling could stratify patients with CD or UC at diagnosis according to their future disease course, and represents a step towards personalised therapy.

Biopsy-derived Intestinal Epithelial Cell Cultures for Pathway-based Stratification of Patients With Inflammatory Bowel Disease

“…Second, steroid-free clinical remission and mucosal healing, two important treatment goals, are observed in no more than 30-35% of patients with large inter-patient variability in treatment response. The search for predictive biomarkers has been unsuccessful so far and as a consequence prediction of therapeutic success is poor6.…”

Classical and recent advances in the treatment of inflammatory bowel diseases

“…The choice of therapy should also be based on the frequency of disease relapse, the extent and severity of disease, and the presence of extra-intestinal manifestations, which indicate serious complications of IBD. Additional factors influence the therapeutic management of the intestinal inflammation, such as the lesion site, activity of the disease and the overall clinical status of each individual patient ( 6 ). Furthermore, though UC and CD share similar clinical features, they may be distinguished by disease location and characteristics of inflammation.…”

“…The first refers to the classical method in which the intensity of treatment increases along with the severity of disease. On the other hand, “top down” strategies include an early onset of intensive treatment such as biological therapies in order to avoid the occurrence of future complications ( 6 ). However, the choice of one of these different approaches by the physician depends on the patient’s responsiveness to prior therapies, clinical condition and the diagnosis.…”

Efeitos da inflamação continuada e do tratamento imunomodulador com anti-TNF no controle da colite experimental

“…Por outro lado, a segunda inicia-se de forma mais intensa, utilizando os imunobiológicos, como um método rápido para conter a inflamação. Em conjuntos essas estratégias terapêuticas visam evitar futuras complicações e/ou recidivas da doença 52 .…”

“…Desse modo, o tratamento das DII depende do equilíbrio entre a eficácia e os efeitos colaterais dos fármacos utilizados, além da frequência de recidiva da doença, extensão, gravidade da inflamação e presença de manifestações extra-intestinais, o que indica complicações graves. Atualmente, várias terapias farmacológicas têm sido majoritariamente indicadas para as DII, como os aminosalicilatos, antibióticos, tiopurinas, antagonistas do ácido fólico 51,52 . Em adição, existem outras abordagens terapêuticas como por exemplo, o uso de células mesenquimais, células tronco hematopoiéticas e anticorpos que neutralizam a ação de citocinas de perfil inflamatório, como os imunobiológicos 51,53 .…”