Introduction

Etrasimod is an oral, selective, synthetic sphingosine 1-phosphate receptor 1, 4, 5 modulator being developed for immune-mediated inflammatory disorders including ulcerative colitis (UC). Below are efficacy and safety results from the 12-week induction period of Study ES101002.

Aims & Methods

ES101002 (NCT04176588) is an ongoing Phase 3, randomized, placebo (PBO) -controlled, double-blind, multicenter, China registrational study aiming to evaluate efficacy and safety of etrasimod 2 mg in patients (pts) with moderately to severely active UC (modified Mayo score 4-9 points, centrally read endoscopic subscore ≥2, and rectal bleeding subscore ≥1) and documented history of inadequate response to, loss of response to, or intolerance to ≥1 UC treatment. The study (re‑randomization design) includes a 12-week Induction (2:1 ratio etrasimod: PBO), a 40-week maintenance period (1:1), and an optional open label period. Permitted concomitant medications include oral 5‑aminosalicylic acid compounds and corticosteroids (prednisone ≤20 mg/day or equivalent). The primary efficacy endpoint is clinical remission; key secondary efficacy endpoints are endoscopic improvement and clinical response. Safety is evaluated throughout the study.

Results

ES101002 is being conducted in mainland China, Taiwan, and South Korea. A total of 340 pts were randomized and dosed for Induction. Baseline demographics and disease characteristics were balanced between groups. All primary and key secondary efficacy objectives were achieved with etrasimod and met statistical significance (P <0.0001) at Week 12 (Table). Moreover, the significant difference in the proportion of etrasimod treated pts achieving symptomatic remission, endoscopic normalization and mucosal healing objectives compared with PBO (Table) demonstrates that treatment with etrasimod results in a concurrent improvement in symptoms of active UC and in the endoscopic and histologic improvement of the mucosa. The percentage of pts reporting ≥1 treatment-emergent adverse event (TEAE) was 67.1% in the etrasimod group and 54.5% in the PBO group. Compared to those taking PBO, a smaller percentage of pts taking etrasimod reported Grade 3 TEAEs, serious TEAEs, and TEAEs leading to study drug discontinuation. The most common TEAE leading to study drug discontinuation was UC worsening (2 pts [0.9%] in the etrasimod group and 2 pts [1.8%] in the PBO group).The most common Grade 3 TEAEs were alanine aminotransferase increased (2 pts [0.9%] in the etrasimod group; no pts in the PBO group) and UC worsening (2 pts [0.9%] in the etrasimod group and 5 pts [4.5%] in the PBO group). No Grade 4 TEAEs or deaths were reported.

Conclusion

Compared to PBO, etrasimod 2 mg treatment showed greater improvement, resulting in clinically meaningful and statistically significant improvement in the primary endpoint and all key secondary endpoints post-Induction. Treatment with etrasimod was safe and well tolerated. The safety profile was consistent with previous studies; no new safety findings were observed.

Introduction

Inflammatory bowel disease (IBD) has a high incidence in young people directly impacting their reproductive years. In 2023, ECCO produced guidelines on sexuality, fertility, pregnancy & lactation to support healthcare professionals in managing patients considering, and throughout pregnancy. This audit undertaken as 3rd year medical student project.

Aims & Methods

The study aimed to evaluate the extent to which ECCO standards on are being met at a tertiary hospital and look at disease activity and adherence to advice.The IBD service was benchmarked against the ECCO guidelines. The women received antenatal care at our linked women’s Hospital. Patients are offered monthly appointments with the IBD team during pregnancy. Data was collected from electronic patient records (EPIC©) of patients under the care of the IBD team. The data were analysed in SPSS using statistical tests, including Mann-Whitney U test.

Results

The study included patients who became pregnant or gave birth between April 1, 2023 - March 31, 2024. The results included 56 women, of whom 28 had already given birth. Thirty women (53.6%) had Crohn’s Disease and 26 (46.4%) had ulcerative colitis. Ages ranged from 20 to 42 years. Forty-eight women (85%) were receiving active treatment, with 23 (41%) on advanced therapies and of these of the 23 people on biologics, 13 (56.6%) continued taking the biologic throughout pregnancy, 6 (26.1%) stopped taking the biologic before the third trimester. 71.4% of women had a documented & individualized care plan. Documentation was noted to be poor around advice re lactation (12.5%).
IBD activity improved between pre-conception and during pregnancy, as indicated by faecal calprotectin levels decreasing on average from 392.7 (SD 630) pre-conception to 104.2 (SD 142.7) during pregnancy. Women with active disease generally give birth earlier than those without active disease, and those with active disease were more likely to have a preterm birth with 25% of the active disease group giving birth prematurely, i.e. before 37 weeks, although this did not meet statistical significance. 50% had a spontaneous vaginal delivery, while 32.2% had a caesarean section. There was no significant difference in the baby’s birth weight between mothers on biologic treatment and those not on biologic treatment.

Conclusion

The audit identified areas where the ECCO standards were not fully met, such as documenting advice around medications and lactation. The IBD team has developed an action plan to address the findings of the audit. We also demonstrated reduced disease activity during pregnancy in this cohort of women and in keeping with previous studies saw that patients with active IBD were more likely to deliver before 37 weeks.

References

1. Torres, J., Chaparro, M., Julsgaard, M., Katsanos, K., Zelinkova, Z., Agrawal, M., Ardizzone, S., Campmans-Kuijpers, M., Dragoni, G., Ferrante, M., Fiorino, G., Flanagan, E., Gomes, C. F., Hart, A., Hedin, C. R., Juillerat, P., Mulders, A., Myrelid, P., O’Toole, A., … van der Woude, C. J. (2023). European Crohn’s and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. Journal of Crohn’s and Colitis, 17(1), 1–27. https://doi.org/10.1093/ecco-jcc/jjac115

Disclosure

No conflict of interest

Introduction

Magnetic resonance enterography (MRE) has superior sensitivity over intestinal ultrasound (IUS) for established small bowel (SB) Crohn’s disease (CD), while retrospective studies suggest small intestinal contrast ultrasound (SICUS) may match computed tomography enteroclysis (CTE) accuracy. The incremental role of SICUS in periodic monitoring of established CD needs further exploration.

Aims & Methods

A prospective study was conducted at a high-volume tertiary gastroenterology center recruiting established CD patients (18-75 years) requiring SB evaluation. The accuracy of IUS followed by SICUS was assessed against CTE/MRE (within 24-48 hours) for detecting active SB disease, extent, bowel wall thickness (BWT), involved length, complications, and impact on management.

Results

A total of 407 patients (median age 36 years, 60.2% male) underwent IUS/SICUS followed by CTE (n=215) or MRE (n=192). SICUS demonstrated a sensitivity of 95.3% and specificity of 93.0% for detecting SB disease. For disease extent, sensitivity was 90.7% and specificity 90.5%. SICUS significantly improved stricture detection as compared to IUS (sensitivity 86.8% vs. 71.3%, p=0.0005). SICUS demonstrated high sensitivity of 91.7% for fistulas, and 87.5% for abscesses. SICUS correlated strongly with CTE/MRE for BWT (Spearman’s rho, R=0.667, p<0.001) and disease length (R=0.839, p<0.001). Missed lesions (n=17) and strictures (n=22) were predominantly in the proximal and mid-SB. Management changed in 9.3% (n=38) following CTE/MRE, primarily for surgical planning (n=8), therapy escalation (n=10), and stricture management (n=6) (table 1).

Conclusion

IUS and SICUS are highly accurate, non-invasive tools for monitoring SB CD, with SICUS improving stricture detection. While CTE/MRE remains essential for evaluating proximal and mid-SB disease and surgical planning, the limited incremental impact reinforces IUS/SICUS as effective first-line modalities (ClinicalTrials.gov: NCT 06125678).

References

Taylor SA, Mallett S, Bhatnagar G, et al; METRIC study investigators. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial. Lancet Gastroenterol Hepatol. 2018 Aug;3(8):548-558. doi: 10.1016/S2468-1253(18)30161-4.

Introduction

Secondary loss of response to Infliximab(IFX) occurs in approximately half of patients with Inflammatory Bowel Disease(IBD), due to drug levels falling below the therapeutic range. This study evaluated IFX levels and related clinical and laboratory parameters and their impact on clinical outcomes.

Aims & Methods

Pre-infusion drug levels, associated laboratory data, and clinical parameters were evaluated in IBD patients receiving maintenance doses of IFX(5–15 mg/kg every 4–8 weeks) between Nov2021-Apr2025. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4–20µg/mL.

Results

A total of 1,059 single pre-infusion measurements from 455 patients and consecutive dual measurements at weeks 4 and 8 from 64 patients were evaluated. In the single and double measurement groups, 75.4% and 84.4% of patients had Crohn’s disease(CD), respectively. The most commonly used doses were 5 mg/8 weeks and 10 mg/4 weeks(Table 1) Drug levels were below 5 µg/mL in 33% of the measurements. Antibody positivity was present in 47.5% of 120 available measurements ranging from 0.4-20 µg/mL, showing no significant correlation with drug levels or immunomodulatory(IM) use (p=0.62 and p=0.61) However, for all positive antibody measurements drug levels were ≤ 3.5 µg/mL. CRP differed significantly across drug level groups, whereas albumin did not(Table 1). A weak negative correlation was found between IFX levels and CRP(r = -0.13, p = 0.001), with no correlation for albumin(p=0.54). In UC patients, the correlation between CRP and IFX levels was slightly stronger(r= -0.280, p=0.004).No significant associations were found between IM use and IFX levels >5 µg/mL(p=0.55), >10 µg/mL(p= 0.93), or >20µg/mL(p = 0.87). Abdominal pain was more common in patients with IFX levels <5 µg/mL (p=0.032) and <10 µg/mL (p=0.044). Smoking status was not associated with achieving IFX levels >5 µg/mL( p=0.57), >10 µg/mL (p=0.89), and >20 µg/mL (p=0.633). Among CD patients, those with IFX levels >5 µg/mL had significantly lower CDAI scores (p = 0.039), and lower daily stool frequency (p=0.002).Regression analysis showed that higher BMI (p=0.045), lower CRP(p < 0.001), higher IFX dose(p < 0.001), and CD diagnosis(p =0.014) to be independently associated with achieving IFX levels >5 µg/mL. These factors also predicted levels >10 µg/mL and >20 µg/mL, except for BMI at the >20 µg/mL threshold. In the dual measurement group, the median CRP levels at weeks 4 and 8 were 2.1(5.1) and 2.5(6.3), respectively (p = 0.108). Among patients with IFX >20 µg/mL at week 4, 75% maintained levels >5 µg/mL at week 8, whereas this rate was 64% for those with levels >10 µg/mL. Only 59.6% of those with >5 µg/mL at week 4 retained >5 µg/mL at week 8(all p <0.001). Week 4 IFX levels was 7.3 times higher than at week 8 for cases within measurable range.

Conclusion

One-third of patients demonstrated sub-therapeutic drug levels, which were associated with elevated CRP levels and worse clinical outcomes. Notably, the 5mg/4 weeks group exhibited higher drug concentrations compared to the 10mg/8 weeks group, suggesting that increased infusion frequency may contribute to achieving higher levels. Moreover, maintaining sufficient drug levels at week 8 requires substantially higher levels at week 4. Measurement of anti-TNF antibodies may not be fruitful if drug level is > 3.5µg/mL. These findings support the drug monitoring and personalized dosing to reduce the risk of loss of response and improve outcomes.