Abstract Background Changes in prevention and treatment strategies of postoperative recurrence (POR) of Crohn’s disease (CD) over recent decades have resulted in improved long-term prognosis. However, it remains unclear whether the role of surgery in the biologic era, advances in surgical techniques, and prior exposure to advanced therapies may have modified the natural history of POR. Our aim was to assess endoscopic (ePOR) and clinical (cPOR) postoperative recurrence over the last three decades in patients with CD who underwent surgical resection without subsequent prophylaxis or treatment. Methods We performed a systematic review and meta-analysis of controlled clinical trials on POR prevention that included a placebo group. Data were collected regarding study design, population characteristics and endoscopic and clinical POR rates in placebo groups. Pooled POR rates were estimated using random effects model and reported as overall proportion from studies reporting a single proportion with 95% confidence intervals. Statistical heterogeneity was assessed by the test and complemented with the index. Leave-one-out sensitivity analysis was performed when high statistical heterogeneity. A subgroup analysis was conducted to estimate the overall effect on follow-up time and year of publication. A meta-regression analysis examined the influence of known risk factors on outcome rate. Results Twenty of 39 identified studies were included. Regarding study design, only one selected a high-risk population, three included first surgeries, four used centralized endoscopy reading, and nineteen the Rutgeerts score. Concerning risk factors, perianal disease rate was available in 2 studies, penetrating phenotype in 7, and smoking status in 12. Prior exposure to immunomodulators was available in 7 studies and to biologics in 13. Among these variables, only the availability of smoking data was lower in pre-2000 studies. No differences were observed in mean disease duration at surgery across the three periods. ePOR and cPOR rates are shown in Table 1. In meta-regression analyses, ePOR risk at 6 months correlated significantly with year of publication (more recent, more risk) (0.07 CI95% 0.01–0.14; p = 0.016), whereas severe ePOR risk at 6 months correlated with year of publication (0.05 CI95% 0.00–0.11; p = 0.039), proportion of active smokers (9.4 CI95% 3.2–16; p = 0.003), and proportion of first resections (–8.3 CI95% –12– –4.1; p 0.001). Conclusion Patients included in RCT for CD POR prevention showed an increased risk of ePOR and severe ePOR over time. Variations in POR are also influenced by the proportion of active smokers and first intestinal resections. Studies with individual data of large prospective cohorts are warranted to unravel the underlying causes. Conflict of interest: Ms. Piñero, Gisela Soledad: GP has served as a speaker or has received education funding or advisory fees from Adacyte, AbbVie, Kern Pharma, Ferring, Alfasigma. Mañosa Ciria, Miriam: Personal Fees: Abbvie, FAES Pharma, Ferring, Jannsen, MSD, Pfizer, Tillots and Lilly Dall’Oglio, Sofía: No conflict of interest Avella, Andrea: No conflict of interest Puig González, Maria: No conflict of interest Gonzalez, Laura: No conflict of interest Calafat Sard, Margalida: Personal Fees: Advisory fees for Gilead Other: I have served as a speaker, or has received research or education funding for Takeda, Janssen, Faes Farma, Falk Pharma, Kern, Pfizer and MSD. Domènech Moral, Eugeni: Personal Fees: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. Other: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Alfasigma/Galapagos Biogen, Celltrion, Ferring, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Takeda, Tillots.
Piñero et al. (Thu,) studied this question.