Society: AGA

BACKGROUND: Prevention of postoperative recurrence (POR) in Crohn’s disease (CD) after ileo-colonic (IC) resection is still a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in presence of at least one clinical risk factor (RF). Due to drug-related adverse events and the relative high cost of biologics, we aimed to determine whether prevention of POR can be postponed and guided by endoscopy in CD patients with only one RF.
METHODS: A multicentre retrospective study was conducted in 12 Italian centres. CD patients with only one RF for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, or active smoking were considered. Patients who performed a colonoscopy between 6 to 12 months after curative IC resection were included. Two groups were formed based on whether immunosuppressive therapy was started immediately after surgery (prophylaxis group) or guided by endoscopy (observation group). Primary endpoints were the rates of any endoscopic recurrence (Rutgeerts ≥i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence (HBI≥5) rates at 6, 12 and 24 months after surgery.
RESULTS: A total of 195 patients were enrolled. Out of all, 61 (31.3%) received immunoprophylaxis at a median time of 32 days [IQR 26-55] after surgery (n=14 infliximab, n=37 adalimumab, n=7 azathioprine, n=3 ustekinumab). Baseline patient characteristics are detailed in Table 1. Particularly, risk factors for POR were homogeneously distributed between the 2 groups. Colonoscopy was performed after a median time of 8 months [IQR 6-11]. No differences between immunoprophylaxis and endoscopy-driven approach was found regarding any endoscopic recurrence (36.1% in prophylaxis group vs 45.5% in observation group, p=0.10) and severe endoscopic recurrence (9.8% in prophylaxis group vs 15.7% in observation group, p=0.15). In 32 patients with a second colonoscopy at a median time of 30.5 months [IQR 22-43.75] after surgery, any recurrence and severe recurrence rates were also similar (p=0.55 and p=0.43, respectively).
Early clinical recurrence at 6 months was reported in 23.4% of patients on immunoprophylaxis vs 31.5% who were not (p=0.43). Clinical recurrence rates between prophylaxis and observation group were also similar at 12 months (17.9% vs 34.8%, respectively, p=0.09) and at 24 months (17.9% vs 24.1%, respectively, p=0.63).
CONCLUSION: In CD patients with only one RF for POR, immediate immunoprophylaxis after curative IC resection does not decrease the rate of early clinical and endoscopic recurrence. Prospective and larger studies are needed to confirm our results.

Background
Early treatment of Crohn’s disease (CD) often involves biologics such as anti-tumor necrosis factor (anti-TNF) agents. Ileocecal resection (ICR), while a therapeutic option in early CD, is generally reserved for complicated CD or when medical treatment fails. We aimed to compare long-term outcomes of ICR and anti-TNF therapy as index treatment for ileocecal CD, initiated within one year of diagnosis, in the Danish nationwide cohort.

Methods
Using cross-linked nationwide registers, we identified all individuals who lived in Denmark and were diagnosed with ileal CD between 2003 and 2018. We included individuals who underwent ICR or received anti-TNF drugs as index treatment for ileocecal CD within one year of diagnosis. We excluded patients who did not have pathology information confirming disease in the ileocecal region. The primary outcome was a composite of CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD diagnosis. We conducted Cox proportional hazards regression analyses to compare outcomes in the two groups after adjusting for potential confounders. We also determined the proportion of individuals initiated on immunomodulator (IMM), anti-TNF, or no therapy at 5 years after ICR.

Results
Of the 16,443 individuals diagnosed with ileocecal CD between 2003 and 2018, 581 (3.5%) and 698 (4.2%) individuals with confirmed disease in the ileocecal region underwent ICR and received anti-TNF as the index treatment, respectively. The composite outcome occurred in 273 individuals (IR 110.3/100,0 person years (PY)) in the ICR group and in 318 individuals (IR 201.9/100,0 PY) in the anti-TNF group. The risk of the composite outcome was 33% lower in the ICR group compared to the anti-TNF group (aHR 0.67; 95% CI 0.54, 0.83), after adjusting for demographic and clinical variables. On analysis of individual outcomes, ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not CD-related hospitalization or perianal CD diagnosis. Of individuals who underwent ICR, the proportion that was initiated on IMM, anti-TNF treatment or no treatment at 5 years of follow up was 47.5%, 17.1%, and 50.3%, respectively.

Conclusion
These data support the role of ICR as an index treatment for ileocecal CD and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Further studies will help identify characteristics of individuals who needed no treatment after ICR.

Background
We aimed to compare the effectiveness of tofacitinib and ustekinumab in patients with ulcerative colitis (UC) previously exposed to at least one anti-TNF agent.
Methods
In this multicenter study, we retrospectively included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) > 2, having who started tofacitinib or ustekinumab between January 2019 and June 2022.
The primary endpoint was steroid-free clinical remission (pMS ≤ 2) (CFREM) at week 16 (W16).
Secondary endpoints were endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and histological remission (CFREM + MES ≤ 1 + Nancy index ≤ 1).
Comparisons were performed using propensity score analyses adjusted on potential confounders.
Results
Overall, 289 patients were included (tofacitinib = 124 patients, ustekinumab = 165 patients). The groups were comparable (tofacitinib vs vedolizumab) for male gender (50.8% vs 43.3%), mean age (40.7 vs 42.9 years), median UC duration (8.6 vs 9.3 years), concomitant use of 5-ASA (13.7% vs 9.7%), steroids (25.0% vs 29.7%), immunosuppressants (7.3% vs 5.5%), and ≥ 2 prior biologics (85.5% vs 82.4%). Tofacitinib group had more pancolitis (55.6% vs 42.4%, p = 0.026) and UC with pMS > 6 (64.5% vs 50.3%, p = 0.016). In our study, 42.1 % of the patients treated with tofacitinib continued using a dose of 10 mgx2/day until W16 while 47.3% of the patients on ustekinumab required dose escalation to 90 mg/4 weeks before W16.
After propensity score analysis, the rate of CFREM at W16 was 37.8% and 35.6% in the tofacitinib and ustekinumab arms, respectively arm (p=0.75). CFREM at W16 was achieved in 43.3% vs 57.1% (p = 0.48) after failure of one biologic, 20.7% vs 37.9% (p=0.16) two biologics and 46.7% vs 23.2% (p=0.047) if ≥ 3 biologics, in tofacitinib and vedolizumab arms, respectively. After primary failure to at least one biologic, the rate of CFREM at W16 was 46.3% on tofacitinib vs 25.9% on ustekinumab (p = 0.13). CFREM at W16 was similar with tofacitinib and ustekinumab in case of more severe UC such as pMS ≥ 6 (40.6% vs 41.5%) and CRP > 30 (27.2% vs 33.0%).
No predictor of tofacitinib effectiveness has been identified. Factors associated with no CFREM at W16 on ustekinumab were male gender (p=0.035), ≥ 3 prior biologics (p=0.013), prior use of tofacitinib (p=0.03), primary failure to at least one biologic (p=0.013).
After propensity score analysis, endoscopic remission was achieved in 17.0% vs 11.7% (p =0.47) and histological remission in 4.4% vs 7.8% (p=0.32) of the patients treated with tofacitinib and ustekinumab, respectively.
Conclusion
Tofacitinib and ustekinumab have similar effectiveness in UC after anti-TNF failure.
However, the efficacy of ustekinumab could be more impacted by prior therapeutic failures.

Bruno Pereira

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