Introduction

The STRIDE II guidelines recognize endoscopic healing as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, transmural healing could reduce the risk of long-term complications. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic and ultrasound healing.

Aims & Methods

We conducted a prospective study that included all patients with CD in clinical remission who underwent colonoscopy with endoscopic healing (CDEIS <4) and intestinal ultrasound (IUS) within 4 weeks between September 2019 and September 2022. IUS transmural healing was defined by a parietal thickness < 3 mm on all digestive segments (colonic and ileal) without color doppler signal.
The primary endpoint was CD relapse, defined as the need for drug intensification, initiation of corticosteroid therapy, CD-related hospitalization, development of a perianal and luminal fistula or abscess, or the need CD-related bowel surgery. Patients were followed up at least every 6 months for two years.

Results

A total of 93 patients were included, the majority of whom were women (53%) with ileocolonic location (43%). The median disease duration was 12 years (IQR, 4-19) and 71% patients were treated with anti-TNF. Ultrasound transmural healing was observed in 73% (68/93) of patients. After a median follow-up of 22.5 months [IQR, 19.3-23.7] 26% of patients have relapsed. The risk of relapse was significantly higher among patients IUS activity at 6 and 12 months (13% vs. 5% and 24% vs 8 % p = 0.007). In multivariate analysis, the risk of relapse was 3 times higher without IUS transmural healing (HR 3.07 (1.35-9.97); p = 0.007). Among patients with a complete endoscopic healing (CDEIS 0) the relapse rate were also significantly higher among patients with IUS activity compared to those with IUS healing (HR 3.65 (1.06-12.8); p =0.040).

Conclusion

IUS transmural healing was associated with a lower risk of relapse among patients with endoscopic healing and could be considered as a non-invasive therapeutic target in CD.

Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by relapsing symptoms and significant impact on quality of life, with current therapies often limited by suboptimal efficacy or adverse effects. Interleukin-12/23p40 (IL-12/23p40) antagonists have emerged as targeted treatments due to their role in modulating key inflammatory pathways, yet the class-wide efficacy and safety of these agents remain uncertain.

Aims & Methods

To evaluate the effectiveness and safety of IL-12/23p40 antagonists in moderate to severe UC, a systematic review, meta-analysis, and trial sequential analysis were conducted. Databases including PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were searched in December 2024 to identify randomized controlled trials (RCTs) comparing IL-12/23p40 antagonists to placebo. Outcomes included clinical and endoscopic remission and response, adverse events, and additional endpoints such as histologic healing, symptomatic relief, and glucocorticoid-free remission. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were pooled using a random-effects model in R software.

Results

Nine RCTs enrolling 3,808 patients in the induction phase and 1,734 in the maintenance phase were included [1–6]. IL-12/23p40 antagonists significantly improved clinical remission during induction (21.8% vs. 8%; RR 2.63, 95% CI 2.05–3.36, p < 0.001) and maintenance (46.8% vs. 23%; RR 1.99, 95% CI 1.63–2.44, p < 0.001), and clinical response (induction: RR 1.94, 95% CI 1.70–2.20, p < 0.001; maintenance: RR 1.51, 95% CI 1.34–1.69, p < 0.001). Endoscopic remission (induction: RR 2.36, 95% CI 1.63–3.41, p < 0.001; maintenance: RR 1.96, 95% CI 1.63–2.37, p < 0.001) and endoscopic response were also significantly improved. Notably, prior biologic or JAK inhibitor failure was linked to higher induction remission rates (RR 3.74, 95% CI 1.60–8.76, p = 0.002), with meta-regression confirming this association (p = 0.008), suggesting enhanced remission in previously treatment-resistant patients. Additionally, IL-12/23p40 antagonists improved histologic, endoscopic, and mucosal healing (RR 2.49; 95% CI 2.01–3.08, p < 0.001), symptomatic remission (RR 2.16, 95% CI 1.66–2.82, p < 0.001), and quality of life as measured by the IBDQ score (MD 16.3, 95% CI 12.2–20.4, p < 0.001). Moreover, IL-12/23p40 antagonists demonstrated a favorable safety profile in both the induction and maintenance phases. During induction, they were associated with a significantly lower risk of serious adverse events (RR 0.40, 95% CI 0.27–0.69, p < 0.001). No significant differences were observed compared to placebo in the overall incidence of adverse events (induction: RR 0.97, 95% CI 0.90–1.04, p = 0.38; maintenance: RR 0.95, 95% CI 0.87–1.03, p = 0.22), headache (induction: RR 1.17, 95% CI 0.82–1.68, p = 0.39; maintenance: RR 1.29, 95% CI 0.60–2.78, p = 0.51), or nasopharyngitis (induction: RR 1.09, 95% CI 0.67–1.76, p = 0.73; maintenance: RR 1.07, 95% CI 0.77–1.50, p = 0.68).

Conclusion

IL-12/23p40 antagonists demonstrate superior efficacy compared to placebo in inducing and maintaining clinical and endoscopic remission in patients with moderate to severe UC, with a favorable safety profile and potential benefits even among biologic-experienced populations. These results support the use of IL-12/23p40 antagonists as an effective and well-tolerated treatment option in the management of UC.

References

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