Biologics in the management of pediatric inflammatory bowel disease: When and what to choose

Abstract

Pediatric inflammatory bowel disease (PIBD) is a chronic inflammatory disorder of the gastrointestinal tract, with rising global incidence and prevalence. Over the past two decades, biologics have added to the therapeutic armamentarium and revolutionized the approach to treatment of inflammatory bowel disease. The available biologics include monoclonal antibodies which target inflammatory cytokines (anti-tumor necrosis factor alpha, anti-interleukin 12/23) or recruitment of leucocytes to the gastrointestinal tract (anti-alpha4beta7 integrin) and small molecules (Janus kinase inhibitors, sphingosine 1-phosphate-inhibitors) which modify the proinflammatory signaling. Considering their potential disease-modifying ability, recent pediatric guidelines from the West have advocated upfront use of biologics in appropriate clinical scenarios as a top-down approach rather than the conventional step-up approach. Although real-world studies are available regarding the clinical efficacy of biologics in PIBD, there is paucity of long-term outcome and safety data in children. Also, little information is available about the best approach in the newly industrialized - developing countries where PIBD is rising but at the same time, infections are prevalent and resources are limited. In this review, we summarize the efficacy and safety profile of biologics and small molecule drugs and discuss the challenges in the management of PIBD, especially in the developing world, and future directions.

Keywords: Biologics; Children; Inflammatory bowel disease; Therapeutic drug monitoring; Dual biologic

Core Tip: Biologics have revolutionized the treatment of pediatric inflammatory bowel disease. The increasing number of biologics (anti-tumor necrosis factor alpha, anti-interleukin 12/23 agents, anti-alpha4beta7 integrin agents) and the arrival of small molecules (Janus kinase inhibitors, sphingosine 1-phosphate-inhibitors), have added to our therapeutic armamentarium. The ultimate objective of therapy is to achieve clinical remission and mucosal healing by providing “personalized therapy” keeping in mind the disease particulars, and selecting the therapy based on the efficacy, cost and safety of the biologics. In this review, we have summarized the recent available literature for guiding the pediatric gastroenterologist about the practical use of biologics and small molecules for children with inflammatory bowel disease.