Introduction

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Clinical Case Summary

27-year-old male with penetrating Crohn's disease (CD; A1, L2, pB3), diagnosed at the age of 9, with multiple hospitalizations. The patient was treated with infliximab + azathioprine for three years. Colonoscopy at 16 years showed pancolitis and was complicated with perforation, being submitted to total colectomy with rectal preservation and ileostomy. Therapy was switched to adalimumab+methotrexate, with partial clinical response. After seven years, due to severe complex fistulizing perianal disease, adalimumab was switched to ustekinumab. After 2 years of Ustekinumab monotherapy, he presented disabling symptoms and developed an enterocutaneous fistula peri-ileostomy. Combination therapy with ustekinumab+vedolizumab was started. The patient still maintained discharge from the enterocutaneous and perianal fistulas. After 1 year, a painful circumferential penile ulcer with swelling and seropurulent discharge was noted. Other causes, namely infections were excluded. Biopsies were performed and revealed non-caseous granulomatous inflammation with lymphocytic and eosinophilic infiltrates, compatible with CD. Topical therapy with tacrolimus ointment was applied, with no response. Ustekinumab+vedolizumab was switched to upadacitinib. There was a substantial improvement of the penile lesion, the enterocutaneous fistula discharge reduced, and perianal symptoms resolved on maintenance therapy with Upadacitinib.
Genital metastatic CD is uncommon and mainly occurs in the setting of colonic involvement and perianal disease. Treatment options for MCD remain underwhelming due to the limited available evidence and varying responses of reported therapeutic methods. Optimization of biologic therapy is mandatory.

References

For this case we'll include:
- Pictures ​of the penile ulcers before and during maintenance therapy with upadacitinib
- Endoscopic evaluation during follow-up
- Histological specimen of colectomy and from multiple endoscopic evaluations performed
- Radiological evidence of perianal and peri-ileostomy enterocutaneous fistula

Introduction

Intestinal ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel disease (IBD). While widely used for long-term assessment, its utility in early response evaluation following biologic therapy initiation or modification remains underexplored.

Aims & Methods

This prospective study aimed to assess early ultrasonographic response at week 6 in ulcerative colitis (UC) and Crohn’s disease (CD) patients undergoing induction, dose escalation, or switching of biologic therapy. A total of 24 patients (mean age: 40.1 ± 12.8 years; 54.2% female) were included. Fourteen patients (58.3%) were initiating biologic treatment, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to another biologic agent. Biologic therapies included infliximab (70.8%), adalimumab (16.7%), and others (12.5%). IUS examination was performed at baseline and at week 6. The following parameters were assessed: bowel wall thickness (BWT), wall stratification, color doppler signal activity and mesenteric fat inflammation. IUS remission was defined as bowel wall thickness less than 3 mm and no color doppler signal. IUS improvement was defined as more than 25% decrease in bowel wall thickness without increase in color doppler signal. IUS activity assesment was performed at the same segment of the bowel at the 6th weeks.

Results

A total of 24 patients were included in the study, with a mean age of 40.1 ± 12.8 years; 13 (54.2%) were female. Seven patients (29.2%) had ulcerative colitis (UC), and 17 (70.8%) had Crohn’s disease (CD). Fourteen patients (58.3%) had newly initiated biologic therapy, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to a different biologic agent. Anti-TNF agents were used in 21 patients (87.5%), including infliximab in 17 (70.8%) and adalimumab in 4 (16.7%). The remaining 3 patients (12.5%) were treated with other biologic agents. At baseline, the most active intestinal segment on IUS was the terminal ileum in CD patients (9 patients, 52.9%) and the sigmoid colon in UC patients (4 patients, 57.1%) (p = 0.021). At week 6, 11 patients (45.8%) showed ultrasonographic improvement, 9 patients (37.5%) had no change, and 4 patients (16.7%) showed worsening. The baseline mean bowel wall thickness (BWT) of the most active segment was 5.5 ± 1.3 mm, which decreased to 4.4 ± 1.7 mm at week 6. A reduction in BWT was observed in 18 patients (75%), while an increase was seen in 6 patients (25%) (p = 0.002). In multivariate regression analysis, higher baseline bowel wall thickness was identified as an independent predictor of ultrasonographic improvement at week 6 (OR: 3.137; 95% CI: 1.005–9.790; p = 0.04). In patients who showed improvement, bowel wall thickness significantly decreased from baseline 6.2 ± 1.5 mm to 3.7 ± 1.6 mm at week 6 (to; p = 0.003), whereas in patients who worsened, an increase in wall thickness was observed (5.3 ± 1.0 mm to 6.7 ± 1.7 mm; p = 0.068). By disease group, 5 of the UC patients (71.4%) showed ultrasonographic improvement, 1 (14.3%) remained unchanged, and 1 (14.3%) worsened. Among CD patients, 6 (35.3%) showed improvement, 8 (47.1%) had no change, and 3 (17.6%) worsened. However, there was no statistically significant difference in response patterns between the UC and CD groups (p = 0.244).

Conclusion

Intestinal ultrasound at week 6 effectively detected early treatment response, with baseline bowel wall thickness emerging as a predictor of improvement. These results support its use in routine early monitoring of IBD patients on biologic therapy.

References

1. Calabrese E, Rispo A, Zorzi F, De Cristofaro E, Testa A, Costantino G, Viola A, Bezzio C, Ricci C, Prencipe S, Racchini C, Stefanelli G, Allocca M, Scotto di Santolo S, D'Auria MV, Balestrieri P, Ricchiuti A, Cappello M, Cavallaro F, Guarino AD, Maconi G, Spagnoli A, Monteleone G, Castiglione F. Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study. Clin Gastroenterol Hepatol. 2022 Apr;20(4):e711-e722.
2. Paredes JM, Moreno N, Latorre P, Ripollés T, Martinez MJ, Vizuete J, Moreno-Osset E. Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn's Disease. Dig Dis Sci. 2019 Sep;64(9):2600-2606.