Editorial: Managing the Moving Target—Dose Adjustments in Inflammatory Bowel Disease

Optimising medical therapy represents a challenge to the modern-day inflammatory bowel disease (IBD) physician, particularly in treating high-risk IBD phenotypes where elevated drug levels are often preferred 1, 2. Despite the expansion of the therapeutic armamentarium, optimised dosing strategies remain understudied. Importance should be placed on maximising the therapeutic benefit of each agent, noting diminishing response rates with successive lines of advanced therapy. This challenge is further complicated by balancing the effectiveness of escalated dosing with the risks of increased drug exposure. Meanwhile, the safety and timing of dose de-escalation remain unclear and must balance the risk of disease flare with the likelihood of recapturing response if loss of response occurs. We congratulate Dr. Rubín de Célix and colleagues on their manuscript which addressed real-world patterns of dose escalation, de-escalation, and re-escalation of biologic therapy in IBD. Using the large Spanish ENEIDA registry, totalling nearly 20,000 patients with IBD, they provided robust estimates of how often biologic dose intensification is needed (~26% overall) and how effective it is at recapturing remission (~50% success across agents). Notably, they extended prior knowledge by examining dose de-escalation outcomes and subsequent re-escalation effectiveness. A key strength of the study is its comprehensive scope, which examined five biologics including newer agents such as vedolizumab and ustekinumab and provided one of the first real-world insights into re-escalation success 3. Detail which was not presented from this registry but is of particular interest is subgroup data according to disease phenotype and therapeutic drug monitoring (TDM). Higher risk phenotypes such as stricturing small bowel Crohn's disease and perianal fistulising Crohn's disease have improved response rates with higher anti-tumour necrosis factor (anti-TNF) trough concentrations 1, 2. It would be interesting to see whether drug failure could be predicted in this registry according to reported drug levels. Other data of interest include the rates of immunomodulator use, particularly for the anti-TNF agents, and their impact on durability and prevention of immunogenicity at this population level. For infliximab, TDM allows for proactive escalation to prevent drug failure (particularly in the induction phase); in the event of disease flare in the presence of supratherapeutic drug concentrations, this may indicate the need for a switch in drug class. Conversely, supratherapeutic drug levels may also afford more confidence in initiating drug de-escalation in an individual exhibiting response to therapy. Notably, the authors demonstrated that rates of remission maintenance following dose de-escalation with vedolizumab (88%) and ustekinumab (75%) were comparable to those seen with infliximab (80%). This pattern of dose adjustments speaks to the trend towards personalised management in IBD with treatment adjusted to therapeutic drug levels, disease phenotype and even patient genotype—such as TPMT and NUDT15 status in the use of thiopurines. As evidence in this space develops, we may move away from standard dosing as the norm, instead using this as a starting point for optimised care. Nicholas Clark: conceptualization, writing – original draft, writing – review and editing. Daniel Tassone: conceptualization, writing – original draft, writing – review and editing. Nik Sheng Ding: conceptualization, writing – original draft, writing – review and editing, supervision. J.D. has served as a speaker and received grants from Janssen, Pfizer, Chiesi, and Abbvie. This article is linked to de Rubín Célix et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70312 and https://doi.org/10.1111/apt.70379. The data that support the findings of this study are available from the corresponding author upon reasonable request.