Introduction

Prevention of postoperative recurrence (POR) after ileocolonic resection is one of the most relevant issues in the management of Crohn's disease (CD). The role of ustekinumab (UST) especially in the context of real-life studies is still not entirely clear, often due to small sample sizes, thus requiring further investigation and confirmation (1).

Aims & Methods

Our real life single-centre retrospective study aims to evaluate the effect of UST therapy on prophylaxis of endoscopic recurrence after ileo-colonic resection in CD. In the whole cohort UST was used as first-line therapy for prophylaxis of recurrence. All patients (pts) underwent the first endoscopic evaluation within 6-12 months after surgery to assess postoperative recurrence (POR), using the Rutgeerts score and were subsequently evaluated at 22 (+-3) months with a second endoscopy. Persistence on therapy ~ two years after the surgery was also evaluated.

Results

27 pts with a mean age of 51 years old were included. 40% of pts had previously been resected and 45% were active smokers. 93% had already been exposed to one or more biological drugs. The most frequent reason for surgery was the presence of stenosing disease. The first postoperative colonoscopy at 6-12 months, showed severe POR (RS score i3 or i4) in 19% of patients, so 11% changed treatment at this time point. Among patients who continued the drug (24 pts), the second endoscopy performed at 22 (+-3) months showed severe POR in 13% of pts, whose treatment was subsequently changed.
At ~ 2 years persistence on therapy in the cohort was 78%, notably endoscopic remission (RS<2) was found in 37%.
No patients discontinued the drug due to adverse effects.

Conclusion

In our real life cohort of complex CD patients, ustekinumab showed high levels of persistence on therapy at the point of time considered, although less than half of the patients achieved endoscopic remission.

References

1- Tursi A, Mocci G, Picchio M, Elisei W, Maconi G. Letter: ustekinumab for the treatment of post-surgical and refractory Crohn's disease. Aliment Pharmacol Ther. 2021 Apr;53(7):859-860. doi: 10.1111/apt.16281. PMID: 33709395.

Disclosure

No

Introduction

Treatment of post-operative recurrence (POR) after ileocolonic resection is one of the most challenging issues in the management of Crohn's disease (CD). The role of ustekinumab (UST), especially in the context of real-world studies, is still not entirely clear, often due to small sample sizes. Recent studies report encouraging results, with endoscopic remission rates even more than 50% of CD patients, but data are quite heterogeneous (1,2).

Aims & Methods

Our retrospective single-centre real-life study aims to evaluate the effect of UST therapy on the treatment of relapse after ileo-colonic resection in CD. In our cohort, UST was used as second-line therapy in case of recurrence or intolerance of previous therapy. All patients underwent endoscopic or radiological re-evaluation up to 18 months after the start of therapy. Endoscopic success, defined as a reduction of at least one point in the Rutgeerts score, or radiological success, defined as improvement in the judgement of the radiologist who performed the examination or the multidisciplinary IBD team at our centre, were evaluated. Persistence in therapy ~ two years after surgery was also assessed.

Results

27 pts with a mean age of 37 years old at surgery were included. 37% of pts had previously been resected and 56% were active smokers. All pts had already been exposed to one or more biological drugs. The most frequent reason for surgery was the presence of stenosing disease. The mean time to start UST therapy since surgery was 21 months.
The reasons for initiation of UST were recurrence of endoscopic and/or radiological disease, or intolerance to previous therapy, Cohort 1 and Cohort 2, respectively.
In Cohort 1 (19 pts) an instrumental re-evaluation was performed after a mean of 14.4 ± 3.3 months following initiation of UST. Endoscopic or radiologic success was reported in 68% 13 of pts, of whom radiologic or endoscopic remission was achieved in 47.3%.
In Cohort 2 (10 pts) an instrumental re-evaluation was performed after a mean of 15.5 ± 3.5 months following initiation of UST, there were no patients who had advanced endoscopic (RS >= 3) and/or severe radiological recurrence of disease at the start of UST in this group. Only one patient showed endoscopic worsening of disease since the start of UST and discontinued treatment. 90% of pts had radiological or endoscopic improvement or stability of disease, of which remission was achieved in 50%.
In the entire cohort (27 pts), persistence on therapy at ~ two years was 74%, and radiological or endoscopic remission in 51%.

Conclusion

In our real life cohort of patients with CD, ustekinumab showed high levels of persistence to therapy at time point considered, with a satisfactory result on endoscopic and/or radiological remission of disease.

References

1-Tursi A, Mocci G, Picchio M, et al. Maconi G.Letter: ustekinumab for the treatment of post-surgical and refractory Crohn’s disease. Aliment Pharmacol Ther. 2021;53:859–860

2-Macaluso FS, Grova M, Mocciaro F, et al. Sicilian Network for Inflammatory Bowel Disease (SN-IBD).Ustekinumab is a promising option for the treatment of post-operative recurrence of Crohn’s disease. J Gastroenterol Hepatol. 2023;38:1503–1509.

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Disclosure

No

Introduction

The prevention of postoperative recurrence (POR) after ileocolonic resection is one of the most relevant issues in the management of Crohn's disease (CD). The role of ustekinumab (UST) and vedolizumab (VEDO) especially in the context of real-life studies is still not entirely clear, often due to small sample sizes, thus requiring further investigation and confirmation.

Aims & Methods

Our real life single-centre retrospective study aims to evaluate the effect of UST and VEDO therapy on prophylaxis of endoscopic recurrence after ileo-colonic resection in CD. In the whole cohort UST or VEDO were used as first-line therapy for prophylaxis of recurrence. All patients (pts) underwent the first endoscopic evaluation within 6-12 months to assess postoperative recurrence (POR), using the Rutgeerts score and were subsequently evaluated at 24 (+-3) months with a second endoscopy. Persistence on therapy two years after the surgery was also evaluated.

Results

64 pts with a mean age of 38 years were included, 25 pts received VEDO (Cohort 1) and 39 UST (Cohort 2).
In the two cohorts, 89% and 91% of pts had been previously resected; 58% and 55% were active smokers. Notably, 100% had already been exposed to one or more biological drugs and the most frequent reason for surgery was the presence of stenosing disease in both cohorts.
In cohort 1, the first post-operative colonoscopy at 6-12 months showed severe POR (RS score >i2) in 28% of pts, all of whom underwent a treatment change at this time point (71% and 29% drug change and VEDO optimisation, respectively). Among the pts who continued the drug (22 pts), the second endoscopy performed at 24 (+-3) months showed severe ROP in 10% of pts, who underwent treatment modification. At ~2 years persistence on therapy in the cohort was 72%.
In cohort 2, the first post-operative colonoscopy at 6-12 months showed severe POR in 25.6% of patients, who changed therapy at this time. Among patients who continued the drug (29 pts), the second endoscopy performed at 24 (+-3) months showed severe POR in 10.3% of pts, who underwent treatment change. At ~2 years persistence on therapy in the cohort was 66.6%. No patients discontinued the drug due to adverse effects in both cohorts.
Comparing the two cohorts regarding severe endoscopic recurrence at 6-12 months and perisistence on therapy at ~2 years, no significant differences emerged between the two groups (p = 1.000, OR: 0.89,IC 95%: 0.29–2.75 and p = 0.86, OR:1.29, IC 95%: 0.43–3.85, respectively).

Conclusion

In our real life cohort of patients with complex CD, ustekinumab and vedolizumab showed high levels of persistence on therapy at ~2 years after surgery. Limited to the small sample population, no significant differences were observed between the two drugs.

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

No

Introduction

Several guidelines for the management of Crohn's disease (CD) recommend surgery in the presence of acute complications. However, in the absence of emergency situations, the optimal time to refer patients for resection surgery has not been established and the impact of delayed surgery remains unclear, especially outside the context of clinical trials.

Aims & Methods

Our study aims to assess the impact of the timing of resection surgery on early endoscopic recurrence. We conducted a single-center, retrospective study evaluating endoscopic outcomes of CD patients who underwent their first ileo-colonic resection. All patients underwent the first endoscopic evaluation within 6-12 months after surgery to assess post-operative recurrence (POR), using the Rutgeerts score (RS), with POR defined as RS ≥ 2.

Results

We included 134 patients. The most frequent reason for surgery was the presence of stenosis. All patients had at least one risk factor for POR, including smoking or penetrating disease. All patients were given prophylactic biological therapy (22% Infliximab, 53% Adalimumab, 8% Vedolizumab and 17% Ustekinumab). POR was observed in 50% of the entire cohort at 6-12 months. No significant difference in POR was found between the drugs administered. The mean time between diagnosis and surgery was 7.35 years +-7.13 years (SD). 52 patients were operated within 2.5 years after diagnosis and 82 afterwards. Comparing the two intervention times, surgery within 2.5 years had a significantly lower endoscopic recurrence rate at 6-12 months (p=0.014, OR: 0.44, 95% CI 0.22, 0.93). This difference remained significant even on multivariate analysis including other risk factors for POR (p=0.022, OR 0.45, 95% CI 0.23, 0.89).

Conclusion

In our real-life cohort, we found that early surgery correlated with a reduced risk of early endoscopic post-operative recurrence. Further prospective analyses on larger cohorts are needed to confirm this finding.

Introduction

Short bowel syndrome (SBS) is a critical clinical condition that occurs when, following multiple intestinal resections, the residual small bowel in continuity is ≤200 cm. SBS is associated with intestinal failure (IF) when the intestinal absorptive function is impaired, requiring intravenous administration of nutritional or electrolyte supplements. Crohn’s disease (CD) is one of the most frequent causes of SBS in adults

Aims & Methods

This study aimed to identify clinical predictive factors of SBS in CD patients (pts). We conducted a prospective study, enrolling consecutive outpatients with CD. Statistical univariate comparison for the primary outcome was assessed for continuous variables by the Mann-Whitney U and the Kruskal-Wallis ANOVA tests. Categorical variables were compared using the chi-square test. We also evaluated a multivariate logistic regression model to identify independent predictors of SBS.

Results

We enrolled 169 pts with CD (47.3% male, mean age 43.5 years [±14.1]). 45.5% of them were smokers; extraintestinal manifestations (EIMs) were present in 45.5% of pts, and 67.5% of pts had bowel resections (26.6% of them with more than one surgery). The median disease duration and median time between diagnosis and the first resection were 9 years (IQR 4-17) and 6.5 years (IQR 1-13), respectively. At baseline, 101 pts were on anti-TNF therapy, and considering the course of the disease, 20.1% of the pts were exposed to ≥3 biologics. 10% of pts had SBS and 5.3% IF. In univariate analysis, comparing patients with and without SBS, the following variables were statistically different: disease duration (p=0.000), upper gastrointestinal disease location (p=0.001), ileocolonic location (p=0.008), stenosing behavior (p=0.040), perianal disease (p=0.000) and time from CD diagnosis to initiation of biological therapy (p=0.002). At multivariate analysis, disease duration (OR 1.2, 95% CI 1.12-1.42, p=0.000) and perianal disease (OR 4.3, 95% CI 0.99-19.27, p=0.050) resulted independently associated with the development of SBS. Conversely, the time from diagnosis of CD to start biological therapy resulted in an inverse association with the onset of SBS (OR 0.8, 95% CI 0.74-0.97, p=0.016). This latter finding could be due to the late use of biological therapy in patients with less severe disease.

Conclusion

Our data identify clinical characteristics allowing gastroenterologists to predict the risk of developing SBS in a cohort of pts with CD. Further studies would be needed to confirm our results.

References

Funded by:2.1 "Rafforzamento e potenziamento della ricerca biomedica del SSN", finanziato dall’Unione europea–NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project "Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets"code:PNRR-MAD-2022-12376791.

Introduction

Endoscopic evaluation offers essential prognostic information in the field of postoperative management of patients with Crohn's disease(CD). Although not validated, the Rutgeerts score is the most widely used. A recent study has introduced the POCER postoperative index (score 0-4), which includes the circumferential extent and depth of anastomotic ulcers.

Aims & Methods

Our study aims to evaluate the POCER Index in a real-life cohort, its correlation with the Rutgeerts score, and its prognostic value of subsequent disease courses.
We conducted a single center, retrospective study evaluating clinical and endoscopic outcomes of patients with CD who underwent ileo-colonic resection. All patients underwent the first endoscopic evaluation within 6-12 months to assess postoperative recurrence(POR). This evaluation was performed using the Rutgeerts score and the POCER Index. POR was defined as Rutgeerts ≥ 2 or POCER ≥ 2. A clinical assessment was performed at 18-24 months for all patients by calculating the Harvey-Bradshaw Index (HBI). A second endoscopic evaluation at 18-24 months was available for a sub-cohort.

Results

We included 103 patients, with a median age at surgery of 38 years old. 79% of the patients had no previous bowel resection surgery history. The main indication for surgery was the presence of stenotic disease. 63% of patients had at least one risk factor for post-surgical recurrence between smoking or penetrating disease. 35 patients were bionaïve (34%). All patients underwent prophylactic biologic therapy (27% with Infliximab, 48% with Adalimumab, 7% with Vedolizumab, and 17% with Ustekinumab. At 6 month, POR was observed in 50 (48.3%) and 17 (16.5%) patients, according to Rutgeerts and POCER scores, respectively. Mean Rutgeerts and POCER scores were 1.39 (± 1.31) and 0.70 (± 1.08); a moderate correlation (r=0.613) between the two was observed. During postoperative follow-up, a sub-cohort of 50 patients underwent further endoscopic examination at 18-24 months. POR was observed in 30 (60%) and 9 (18%) patients, according to Rutgeerts and POCER scores, respectively. Mean Rutgeerts and POCER scores were 1.82 (± 1.34) and 0.86 (± 1.02); a moderate correlation (r=0.571) between the two was observed. Finally, we assessed the ability of Rutgeerts and POCER scores at 6-12 months to predict subsequent clinical relapse (HBI ≥ 5) at 18-24 months. A Rutgeerts score ≥ 2 predicted subsequent clinical relapse with an AUROC of 0.781 (sensitivity 88.24% and specificity 58.82%), while a POCER score ≥ 2 predicted subsequent clinical relapse with an AUROC of 0.714 (sensitivity 35.29% and specificity 86.42%). Interestingly, when evaluating the performance of the combination of the two scores (mean of Rutgeerts + POCER score), we observed that a mean score ≥ 1.5 could predict subsequent clinical relapse with an AUROC of 0.768 (sensitivity 88.24% and specificity 67.06%).

Conclusion

Rutgeerts and POCER score can be used to assess POR and they show only moderate correlation between each other. In predicting subsequent clinical relapse, the Rutgeerts score appears to have greater sensitivity, while the POCER score seems to have greater specificity. The combination of the two might outperform each of them with a good compromise between sensitivity and specificity.

Disclosure

The authors declare no conflict of interest.