Editorial: Managing the Moving Target—Dose Adjustments in Inflammatory Bowel Disease. Authors' Reply

We appreciate the thoughtful contribution of Drs. Clark, Tassone, and Ding [1]. This has added valuable context to our publication on dose adjustment strategies across biologics in inflammatory bowel disease (IBD), using the nationwide ENEIDA registry [2]. They highlighted the importance of optimising biologic therapy in real-world practice, especially in high-risk groups such as patients with multiple treatment failures or those with perianal disease or stricturing behaviour. As noted, a major strength of our study was its comprehensive scope, including the incorporation of newer agents such as vedolizumab and ustekinumab. These real-world data are especially relevant given the growing emphasis on treatment individualisation and the need to understand how these biologics behave outside of clinical trials. Moreover, we identified predictive factors of relapse and therapy discontinuation, which may be key in the management of patients with refractory IBD. Our findings underlined that dose escalation is frequently needed for all biologics over time and is generally effective, with good clinical response and treatment persistence. Although less frequently applied, dose de-escalation maintained disease control in many cases, and re-escalation was successful for most patients who relapsed [1]. We appreciate the interest in further stratification by disease phenotype and therapeutic drug monitoring (TDM). We acknowledge that high-risk patients, such as those with stricturing small bowel Crohn's disease or perianal fistulising Crohn's disease, may have improved response rates with higher anti-tumour necrosis factor (anti-TNF) trough concentrations, as immunogenicity is a mechanism of loss of response [3-5]. However, TDM was not systematically performed in our cohort, and drug levels were not available within the ENEIDA registry. Future studies will aim to explore these dimensions in greater depth, including the role of combination therapy with immunomodulators and the potential influence of TDM-guided strategies. Regarding de-escalation, we agree that supratherapeutic drug levels may provide support when considering dose reduction in patients in sustained remission [6]. In this line, our findings suggested that de-escalation can be considered in selected patients. However, while several studies have demonstrated the potential benefits of TDM in optimising anti-TNF levels before deciding on dose de-escalation, the specific guidelines for implementing this proactive strategy are still not well defined [7]. The current evidence supporting proactive TDM remains limited, with few high-quality studies and small patient cohorts. Significant variability exists in drug and anti-drug antibody assays, therapeutic thresholds, and interpretation of results [6]. In addition, in patients relapsing after dose de-escalation, re-escalation was generally effective in our cohort. Nevertheless, the long-term durability of response after re-escalation remains an area of investigation [8]. In summary, we value the authors' thoughtful perspective on our findings and their shared focus on improving personalised management of IBD. We agree that future efforts should focus on integrating clinical, pharmacokinetic, and multiomic data to better define treatment strategies, improve patient outcomes, and optimise the use of existing IBD therapies. Cristina Rubín de Célix: conceptualization, writing – original draft, writing – review and editing, project administration, methodology, validation. Javier P. Gisbert: conceptualization, writing – review and editing, validation, methodology, project administration. María Chaparro: conceptualization, writing – review and editing, validation, project administration, methodology. The authors' declarations of personal and financial interests are unchanged from those in the original article [2]. This article is linked to Rubin de Celix et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70312 and https://doi.org/10.1111/apt.70340. The data that support the findings of this study are available from the corresponding author upon reasonable request.