Abstract Background The impact of appendectomy on inflammatory bowel disease (IBD) risk remains controversial. In this study, we applied target-trial emulation to mimic a randomized controlled trial (RCT) to clarify the effect of appendectomy on IBD incidence. Methods The emulated target trial was conducted within a large-scale prospective cohort study. We compared participants who underwent appendectomy after the baseline assessment and between 2007 and 2017 with those who were eligible for the procedure but did not undergo it on their assigned index dates. For the appendectomy group, the earliest recorded date of appendectomy was designated as the index date. Each non-surgical participant was randomly assigned five potential index dates sampled from the appendectomy group, with the earliest date on which the participant met all eligibility criteria being selected as the definitive index date. We excluded individuals with a diagnosis of IBD before the index date. Outcomes were defined as incident Crohn’s disease (CD) and ulcerative colitis (UC). To balance baseline characteristics and approximate randomization, we applied overlap weighting based on propensity scores. Weighted Cox proportional hazards models with overlap weights were used to estimate hazard ratios (HRs) for the association between appendectomy and the risk of CD and UC (Figure 1). As a sensitivity analysis, an alternative 1: 4 nearest-neighbours propensity score-matched design was applied to assess the robustness of the findings. Results A total of 432,859 participants eligible for appendectomy were included, of whom 2,365 (0.55%) underwent appendectomy. During a mean follow-up of 11.4 years, 928 incident CD and 2,418 incident UC cases were documented. The appendectomy group contributed nine CD and nine UC cases, while the non-surgical group accounted for 919 CD and 2,409 UC cases. After overlap weighting achieved adequate covariate balance (Figure 2A), we found that appendectomy group exhibited a significantly higher risk of CD (HR 2.05, 95% CI 1.75-2.39) but a lower risk of UC (HR 0.79, 95% CI 0.66-0.95) compared with the non-surgical group (Figure 2B). The main findings of the study were supported by the sensitivity analysis using propensity score matching, which yielded an HR of 2.20 (95% CI 1.88-2.57) for CD and an HR of 0.82 (95% CI 0.70-0.97) for UC (Figure 2B). All P values for interaction were greater than 0.05 in subgroup analyses (Figure 2C). Conclusion In the absence of RCTs, these findings offer the strongest real-world evidence to suggest opposing effects of appendectomy on the incidence of CD and UC. Our findings underscore the need to elucidate the underlying mechanisms, promising to guide surgical decisions for individuals at elevated risk of IBD. Conflict of interest: Ruan, Xixian: I disclose no relevant conflict of interest. Wen, Xiaoyan: Have no conflict of interest. Jing, Fangmin: No financial conflicts of interest Dr. Chen, Jie: No conflict of interest Wang, Xiaoyan: I have no conflict of interest to disclosure.
Ruan et al. (Thu,) studied this question.