Editorial: The Devil Is in the Detail—Interpreting the Findings of Network Meta‐Analyses. Authors' Reply

We thank Drs. Riggott and Gracie for their thoughtful editorial [1], which accompanied our network meta-analysis (NMA) of advanced therapies in Crohn's disease (CD) [2]. We are pleased to see their engagement with our findings and their emphasis on having trials comparing the efficacy of different medical therapies used in CD. We appreciate their recognition of subgroup analyses that we performed, particularly regarding biologic-exposed and -naïve patients. We agree that such analyses are essential to improve the clinical relevance of our NMA. Furthermore, we concur that ongoing and future head-to-head RCTs are important to validate and refine NMA-based insights. However, given the pace of therapeutic development and the logistical challenges of direct comparisons across all therapies, NMAs remain vital to guide clinicians and inform personalised treatment pathways in patients with CD [3, 4]. We acknowledge all the limitations outlined in the editorial, such as differences in trial design, permitted background therapies and maintenance trial structures. We also understand that these factors might introduce complexity in the interpretation of our findings. However, this is the best that can be done with the available data. We performed subgroup analyses where data permitted, including by study design (treat-through vs. re-randomization), to improve the robustness and transparency of our conclusions [2]. We agree that, while pooled analyses provide a broad perspective, detailed evaluation of such subgroups remains essential [5]. For this reason, we encourage readers to review both the main and the Supporting Information in parallel. Drs. Riggott and Gracie correctly note that pooling across studies with differing maintenance trial design may introduce bias. However, our findings align with prior high-quality NMAs in the field [3, 6, 7]. Again, we reiterate that our findings should be interpreted with caution as mentioned in our discussion section [2]. Finally, we echo the call for more head-to-head RCTs to guide optimal sequencing of therapies in CD. Until such data are available, we hope our study provides a helpful evidence-based reference to guide clinicians in their practice. Mohammad Shehab: conceptualization, writing – original draft. Amro Hassan: writing – original draft. Talat Bessissow: supervision, writing – review and editing. This article is linked to Shehab et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70295 and https://doi.org/10.1111/apt.70324. The data that support the findings of this study are available from the corresponding author upon reasonable request.