Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases

Abstract

The past decade has brought substantial advances in the management of inflammatory bowel diseases (IBD). The introduction of tumor necrosis factor (TNF) antagonists, evidence for the value of combination therapy, the recognition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The therapeutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn’s disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older’ anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severity and response to therapy.

Keywords: Inflammatory bowel disease; Small molecule; Positioning; Biologic; Therapeutic

Core tip: Anti-tumor necrosis factor therapy should be considered as first-line therapy in patients with complicated Crohn’s disease and in acute-severe ulcerative colitis. Beyond these specific circumstances, the positioning of novel biologics and small molecules depends on the patient’s medical history, preference and disease phenotype. The efficacy and safety of using immunomodulatory therapy can be enhanced by adhering to therapeutic algorithms and using a ‘treat-to-target’ approach. The risks for adverse events due to poor disease control outweigh the risks associated with early aggressive therapy. In the setting of clinical and biochemical remission, following at least 6 mo of combined immunosuppressive therapy, consideration can be made to withdrawing thiopurine therapy in the correct patient with close follow-up.