Timely Use of Biologics in Early Crohn’s Disease: The Return of “Hit Hard and Early”?

Excerpt

Crohn’s disease (CD) has long been recognized as a destructive and disabling inflammatory bowel disease, leading to progressive and cumulative bowel damage [1], encompassing strictures, fistulas, and/or abscesses. Almost 20% of patients with CD experience penetrating or stricturing complications within 90 days of diagnosis, whereas half of patients will eventually experience these complications 20 years after diagnosis [2]. These complications often require bowel resection, leading to inherent additional bowel damage. Moreover, postoperative recurrence is frequent and may lead to further surgical bowel resection. Current “treat-to-target” strategies aim at avoiding long-term bowel damage and subsequent disability by using disease-modifying therapy in high-risk patients, followed by closely monitoring and adjusting treatment according to a predefined objective goal. Consequently, therapeutic targets have progressively shifted from focusing on clinical outcomes to achieving “deep remission,” including clinical remission combined with mucosal healing [3]. In this respect, anti-tumor necrosis factor (anti-TNF) therapy reverses or at least slows the development of bowel damage [4, 5]. The concept of a “therapeutic window of opportunity” in early CD is growing, as an international expert opinion process developed the Paris definition of early CD for use in future disease modification trials, based on the duration of disease after diagnosis (≤ 18 months) and previous use of disease-modifying agents (no previous or current use of immunomodulators and/or biologics) [6]. Whether the timing of initiating biologic therapy impacts the long-term progressive course of CD remains unclear. Yet, since the presence of bowel damage in early CD is associated with an inferior outcome, with increased risks of surgery and hospitalization [7], the premise for early aggressive treatment is compelling. …