Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis

Abstract

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Keywords: Ulcerative colitis, Infliximab, Adalimumab, Anti-tumor necrosis factor, Predictors of response, Personalized treatment

Core tip: The use of anti-tumor necrosis factor (TNF) monoclonal antibodies for the treatment of ulcerative colitis has been associated with high rates of primary and secondary non-response, important safety issues and considerable cost. Selection of patients with the highest probability to response to anti-TNF treatment would overcome these problems. Analysis of the pivotal trials and accumulated experience from clinical practice has led to the identification of certain prognostic factors for favorable or adverse outcomes. These include clinical and epidemiological parameters, biological markers of inflammation, endoscopic findings, molecular signatures and pharmacological factors. Incorporation of such predictors into the current therapeutic protocols may lead to the optimization of anti-TNF treatment in ulcerative colitis.