Introduction
Despite significant advancements in medical therapy, surgery remains a common option for managing Crohn's disease (CD), especially in cases of complicated disease, with a 10-year risk of surgical resection (SR) of approximately 50%. (1)
Furthermore, it is well-established that the majority of patients experience subsequent relapse after surgery, with up to 90% develop endoscopic post-operative recurrence (POR) within one year. (2)
Several guidelines for managing post-operative CD recommend using pre-operative risk factor stratification to determine the use of prophylactic biologic therapy against POR in high-risk individuals. However, the optimal timing for initiating biologic therapy after resection surgery has not been established, and the impact of a delayed start remains unclear, particularly outside the context of clinical trials. A recent study demonstrated that initiating an anti-TNF agent within 4 weeks after SR was associated with a reduction in POR. (3) However, the comparison was made against patients receiving no prophylaxis with biologic drugs.
Aims & Methods
Our study aims to assess the impact of the timing of biologic therapy initiation on endoscopic recurrence after resection surgery in CD. We conducted a single-center, retrospective study evaluating endoscopic outcomes of CD patients who underwent ileo-colonic resection. All patients underwent their first endoscopic evaluation within 6-12 months after surgery to assess POR, using the Rutgeerts score (RS), with POR defined as RS ≥ 2. All patients received biological therapy for recurrence prevention within 16 weeks after surgery.
Results
We included 177 patients, with a median age at surgery of 38 years old. The primary indication for surgery was stenotic disease. 77% of patients had no prior history of bowel resection and 38% were bio-naive. All patients had at least one risk factor for post-surgical recurrence, including smoking or penetrating disease. Prophylactic biologic therapy (22% Infliximab, 53% Adalimumab, 8% Vedolizumab, and 17% Ustekinumab) was administered to all patients, with initiation within 4 weeks, 4-8 weeks, 8-12 weeks, and 12-16 weeks in 20%, 32%, 15%, and 33% of patients, respectively. POR was observed in 50% of the entire cohort at 6-12 months.
Starting therapy within 12 weeks following SR was associated with a significantly lower recurrence rate than initiating therapy beyond 12 weeks (POR: 36% vs 64% p<0.01).
Notably, induction within 8 weeks showed a lower recurrence rate than after 8 weeks (POR: 39% vs 61%; p < 0.05). There was no significant difference in recurrence rate between starting therapy within 4 weeks and 8 weeks, even when stratifying by risk factors for recurrence. Furthermore, for patients already on biologic therapy prior to SR, therapy was either maintained unchanged, switched, or swapped in 54%, 18%, and 28% of patients, respectively. Investigating the impact of these strategies on POR, we noted significant differences, with less recurrence for those who continued the same therapy after SR (POR: 42% vs 61% vs 72%; p<0.05). However, the mean time to therapy resumption in this group was also significantly shorter than in the others (weeks 9.7 vs 15 vs 13; p< 0.05).
Conclusion
In our a real-life cohort, we found that prophylaxis administered within 12 weeks after resection correlates more strongly with a reduced risk of post-operative recurrence. Furthermore, in this group, our results indicate a lower risk of recurrence in patients receiving prophylaxis within 8 weeks. However, larger clinical studies are needed to confirm these results.
References
1-Frolkis AD, Dykeman J, Negrón ME, Debruyn J, Jette N, Fiest KM, Frolkis T, Barkema HW, Rioux KP, Panaccione R, Ghosh S, Wiebe S, Kaplan GG. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 2013 Nov;145(5):996-1006. doi: 10.1053/j.gastro.2013.07.041. Epub 2013 Jul 27. PMID: 23896172.
2-Bobanga ID, Bai S, Swanson MA, Champagne BJ, Reynolds HJ, Delaney CP, Barksdale EM Jr, Stein SL. Factors influencing disease recurrence after ileocolic resection in adult and pediatric onset Crohn's disease. Am J Surg. 2014 Oct;208(4):591-6. doi: 10.1016/j.amjsurg.2014.06.008. Epub 2014 Jul 18. PMID: 25110291.
3-Axelrad JE, Li T, Bachour SP, Nakamura TI, Shah R, Sachs MC, Chang S, Hudesman DP, Holubar SD, Lightner AL, Barnes EL, Cohen BL, Rieder F, Esen E, Remzi F, Regueiro M, Click B. Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn's Disease Following Ileocecal Resection. Inflamm Bowel Dis. 2023 Jun 1;29(6):888-897. doi: 10.1093/ibd/izac158. PMID: 35905032; PMCID: PMC10233395.
Disclosure
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